Showing papers in "Diabetes Therapy in 2018"
TL;DR: These results demonstrate that a novel metabolic and continuous remote care model can support adults with T2D to safely improve HbA1c, weight, and other biomarkers while reducing diabetes medication use.
Abstract: Carbohydrate restriction markedly improves glycemic control in patients with type 2 diabetes (T2D) but necessitates prompt medication changes. Therefore, we assessed the effectiveness and safety of a novel care model providing continuous remote care with medication management based on biometric feedback combined with the metabolic approach of nutritional ketosis for T2D management. We conducted an open-label, non-randomized, controlled, before-and-after 1-year study of this continuous care intervention (CCI) and usual care (UC). Primary outcomes were glycosylated hemoglobin (HbA1c), weight, and medication use. Secondary outcomes included fasting serum glucose and insulin, HOMA-IR, blood lipids and lipoproteins, liver and kidney function markers, and high-sensitivity C-reactive protein (hsCRP). 349 adults with T2D enrolled: CCI: n = 262 [mean (SD); 54 (8) years, 116.5 (25.9) kg, 40.4 (8.8) kg m2, 92% obese, 88% prescribed T2D medication]; UC: n = 87 (52 (10) years, 105.6 (22.15) kg, 36.72 (7.26) kg m2, 82% obese, 87% prescribed T2D medication]. 218 participants (83%) remained enrolled in the CCI at 1 year. Intention-to-treat analysis of the CCI (mean ± SE) revealed HbA1c declined from 59.6 ± 1.0 to 45.2 ± 0.8 mmol mol−1 (7.6 ± 0.09% to 6.3 ± 0.07%, P < 1.0 × 10−16), weight declined 13.8 ± 0.71 kg (P < 1.0 × 10−16), and T2D medication prescription other than metformin declined from 56.9 ± 3.1% to 29.7 ± 3.0% (P < 1.0 × 10−16). Insulin therapy was reduced or eliminated in 94% of users; sulfonylureas were entirely eliminated in the CCI. No adverse events were attributed to the CCI. Additional CCI 1-year effects were HOMA-IR − 55% (P = 3.2 × 10−5), hsCRP − 39% (P < 1.0 × 10−16), triglycerides − 24% (P < 1.0 × 10−16), HDL-cholesterol + 18% (P < 1.0 × 10−16), and LDL-cholesterol + 10% (P = 5.1 × 10−5); serum creatinine and liver enzymes (ALT, AST, and ALP) declined (P ≤ 0.0001), and apolipoprotein B was unchanged (P = 0.37). UC participants had no significant changes in biomarkers or T2D medication prescription at 1 year. These results demonstrate that a novel metabolic and continuous remote care model can support adults with T2D to safely improve HbA1c, weight, and other biomarkers while reducing diabetes medication use. NCT02519309. Virta Health Corp. Treatments for type 2 diabetes (T2D) have improved, yet T2D and being overweight are still significant public health concerns. Blood sugar in patients with T2D can improve quickly when patients eat significantly fewer dietary carbohydrates. However, this demands careful medicine management by doctors, and patients need support and frequent contact with health providers to sustain this way of living. The purpose of this study was to evaluate if a new care model with very low dietary carbohydrate intake and continuous supervision by a health coach and doctor could safely lower HbA1c, weight and need for medicines after 1 year in adults with T2D. 262 adults with T2D volunteered to participate in this continuous care intervention (CCI) along with 87 adults with T2D receiving usual care (UC) from their doctors and diabetes education program. After 1 year, patients in the CCI, on average, lowered HbA1c from 7.6 to 6.3%, lost 12% of their body weight, and reduced diabetes medicine use. 94% of patients who were prescribed insulin reduced or stopped their insulin use, and sulfonylureas were eliminated in all patients. Participants in the UC group had no changes to HbA1c, weight or diabetes medicine use over the year. These changes in CCI participants happened safely while dyslipidemia and markers of inflammation and liver function improved. This suggests the novel care model studied here using dietary carbohydrate restriction and continuous remote care can safely support adults with T2D to lower HbA1c, weight, and medicine use.
246 citations
TL;DR: There has been an increase in the prevalence of DM in Nigeria, with the highest prevalence seen in the south-south geopolitical zone, and urban dwelling, physical inactivity, advanced age, and unhealthy diet are important risk factors for DM among Nigerians.
Abstract: There has been no nationwide health (diabetes) survey in Nigeria since 1992, when a diabetes mellitus (DM) prevalence of 2.2% was reported. We aimed to determine the prevalence of and risk factors for DM in Nigeria by performing a systematic review and meta-analysis. We searched Medline, EMBASE, PubMed, PapersFirst, the Cochrane Library, Scopus, Bioline, African Journals Online, Institute of Scientific Information, and Google Scholar from the year 1990 to 2017. Using MeSH headings, the terms “diabetes mellitus,” “risk factors,” “prevalence,” and “Nigeria” as well as variations thereof were searched for. The last search was performed on 26 November 2017. We only included studies that utilized the random plasma glucose test, the fasting plasma glucose test, the oral glucose tolerance test (OGTT), or HbA1c to diagnose DM. A total of 23 studies (n = 14,650 persons) were evaluated. A random effects model was used to estimate the pooled prevalence of DM. We estimated the overall pooled prevalence of DM and subgroup-specific DM prevalences while accounting for inter-study and intra-study variability/heterogeneity. The overall pooled prevalence of DM was 5.77% (95% CI 4.3–7.1). The pooled prevalences of DM in the six geopolitical zones of Nigeria were 3.0% (95% CI 1.7–4.3) in the north-west, 5.9% (95% CI 2.4–9.4) in the north-east, 3.8% (95% CI 2.9–4.7) in the north-central zone, 5.5% (95% CI 4.0–7.1) in the south-west, 4.6% (95% CI 3.4–5.9) in the south-east, and 9.8% (95% CI 7.2–12.4) in the south-south zone. Risk factors for the pooled prevalence of DM were a family history of DM (4.6%; 95% CI 3.5–5.6); urban dwelling (6.0%; 95% CI 4.3–7.8); unhealthy dietary habits (8.0%; 95% CI 5.4–10.5); cigarette smoking (4.4%; 95% CI 1.3–10.2); older age (6.6%; 95% CI 4.5–8.7); physical inactivity (4.8%; 95% CI 3.2–6.4); and obesity (5.3%; 95% CI 3.8–6.9). There has been an increase in the prevalence of DM in Nigeria. All regions of the country have been affected, with the highest prevalence seen in the south-south geopolitical zone. Urban dwelling, physical inactivity, advanced age, and unhealthy diet are important risk factors for DM among Nigerians. A national diabetes care and prevention policy is highly recommended.
117 citations
TL;DR: A comprehensive review of diabetic gastroparesis, defined as delayed or disordered gastric emptying, including basic principles and current trends in management, includes sections on anatomy and physiology, diagnosis and differential diagnosis as well as management and current guidelines for treatment.
Abstract: This article is a comprehensive review of diabetic gastroparesis, defined as delayed or disordered gastric emptying, including basic principles and current trends in management. This review includes sections on anatomy and physiology, diagnosis and differential diagnosis as well as management and current guidelines for treatment of diabetic gastroparesis. Diabetic gastroparesis (DGp) is a component of autonomic neuropathy resulting from long-standing poorly controlled type 1 and type 2 diabetes. The diagnostic workup of DGp first excludes obstruction and other causes including medications that may mimic delayed/disordered gastric emptying. Targeting nutrition, hydration, symptomatic relief and glycemic control are mainstays of treatment for DGp. Additionally, optimal treatment of DGp includes good glycemic management, often involving customizing insulin delivery using basal-bolus insulin and technology, including sensor-augmented pumps and continuous glucose monitoring systems. Prokinetic medications may be helpful in DGp symptoms, although only limited number of medications is currently available in the USA. Selected medication-refractory patients with DGp may benefit from gastric neuromodulation, and some from surgical interventions including pyloric therapies that can also be done endoscopically. As is true of any of the diabetic complications, prevention of DGp by early and optimal glycemic control is more cost-effective.Funding: Hansa Medcell, India.
97 citations
TL;DR: Although surreptitious metformin use impacted the primary analysis, reductions in blood glucose and body weight were observed with ertugliflozin in patients with T2DM and stage 3 CKD; ertUGliflozar had an acceptable safety profile.
Abstract: Ertugliflozin is a sodium-glucose cotransporter 2 inhibitor in development for type 2 diabetes mellitus (T2DM). The safety and efficacy of ertugliflozin were evaluated over 52 weeks in patients with chronic kidney disease (CKD). In this double-blind randomized study (NCT01986855), patients with glycated hemoglobin (A1C) 7.0–10.5% and stage 3 CKD [estimated glomerular filtration rate (eGFR) ≥ 30 to < 60 mL/min/1.73 m2] who were undergoing treatment with standard diabetes therapy (or therapies) including insulin and/or sulfonylureas were randomized to once-daily ertugliflozin 5 mg, 15 mg, or placebo. Patients on metformin underwent a pre-randomization ≥ 10-week wash-off period. The primary endpoint was change from baseline in A1C at week 26 in the overall cohort. Secondary efficacy endpoints were assessed in the stage 3A CKD cohort (eGFR ≥ 45 to < 60 mL/min/1.73 m2) at weeks 26 and 52. Safety was assessed in the overall cohort. 468 patients were randomized (baseline mean A1C 8.2%). At week 26, reductions from baseline in A1C were observed across groups in the overall cohort [least squares mean changes (95% confidence interval) – 0.3% (– 0.4, – 0.1), – 0.3% (– 0.4, – 0.1), and – 0.4% (– 0.6, – 0.3) for placebo and for ertugliflozin 5 mg and 15 mg, respectively]. Prohibited use of metformin was identified in ~ 17% of patients and impacted evaluation of the primary endpoint. Greater reductions from baseline in body weight, fasting plasma glucose, and systolic blood pressure were observed with ertugliflozin versus placebo at week 26 (stage 3A CKD cohort). The incidences of urinary tract infections, genital mycotic infections, and hypoglycemia adverse events were not meaningfully different between groups. The incidence of hypovolemia-related adverse events was higher with ertugliflozin relative to placebo. Although surreptitious metformin use impacted the primary analysis, reductions in blood glucose and body weight were observed with ertugliflozin in patients with T2DM and stage 3 CKD; ertugliflozin had an acceptable safety profile. Merck Sharp & Dohme Corp. a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA and Pfizer Inc. Clinicaltrials.gov identifier NCT01986855.
96 citations
TL;DR: Indications for exogenous insulin therapy in patients with type 2 diabetes mellitus (T2DM) include acute illness or surgery, pregnancy, glucose toxicity, contraindications to or failure to achieve goals with oral antidiabetic medications, and a need for flexible therapy.
Abstract: A diagnosis of diabetes or hyperglycemia should be confirmed prior to ordering, dispensing, or administering insulin (A). Insulin is the primary treatment in all patients with type 1 diabetes mellitus (T1DM) (A). Typically, patients with T1DM will require initiation with multiple daily injections at the time of diagnosis. This is usually short-acting insulin or rapid-acting insulin analogue given 0 to 15 min before meals together with one or more daily separate injections of intermediate or long-acting insulin. Two or three premixed insulin injections per day may be used (A). The target glycated hemoglobin A1c (HbA1c) for all children with T1DM, including preschool children, is recommended to be < 7.5% (< 58 mmol/mol). The target is chosen aiming at minimizing hyperglycemia, severe hypoglycemia, hypoglycemic unawareness, and reducing the likelihood of development of long-term complications (B). For patients prone to glycemic variability, glycemic control is best evaluated by a combination of results with self-monitoring of blood glucose (SMBG) (B). Indications for exogenous insulin therapy in patients with type 2 diabetes mellitus (T2DM) include acute illness or surgery, pregnancy, glucose toxicity, contraindications to or failure to achieve goals with oral antidiabetic medications, and a need for flexible therapy (B). In T2DM patients, with regards to achieving glycemic goals, insulin is considered alone or in combination with oral agents when HbA1c is ≥ 7.5% (≥ 58 mmol/mol); and is essential for treatment in those with HbA1c ≥ 10% (≥ 86 mmol/mol), when diet, physical activity, and other antihyperglycemic agents have been optimally used (B). The preferred method of insulin initiation in T2DM is to begin by adding a long-acting (basal) insulin or once-daily premixed/co-formulation insulin or twice-daily premixed insulin, alone or in combination with glucagon-like peptide-1 receptor agonist (GLP-1 RA) or in combination with other oral antidiabetic drugs (OADs) (B). If the desired glucose targets are not met, rapid-acting or short-acting (bolus or prandial) insulin can be added at mealtime to control the expected postprandial raise in glucose. An insulin regimen should be adopted and individualized but should, to the extent possible, closely resemble a natural physiologic state and avoid, to the extent possible, wide fluctuating glucose levels (C). Blood glucose monitoring is an integral part of effective insulin therapy and should not be omitted in the patient's care plan. Fasting plasma glucose (FPG) values should be used to titrate basal insulin, whereas both FPG and postprandial glucose (PPG) values should be used to titrate mealtime insulin (B). Metformin combined with insulin is associated with decreased weight gain, lower insulin dose, and less hypoglycemia when compared with insulin alone (C). Oral medications should not be abruptly discontinued when starting insulin therapy because of the risk of rebound hyperglycemia (D). Analogue insulin is as effective as human insulin but is associated with less postprandial hyperglycemia and delayed hypoglycemia (B). The shortest needles (currently the 4-mm pen and 6-mm syringe needles) are safe, effective, and less painful and should be the first-line choice in all patient categories; intramuscular (IM) injections should be avoided, especially with long-acting insulins, because severe hypoglycemia may result; lipohypertrophy is a frequent complication of therapy that distorts insulin absorption, and therefore, injections and infusions should not be given into these lesions and correct site rotation will help prevent them (A). Many patients in East Africa reuse syringes for various reasons, including financial. This is not recommended by the manufacturer and there is an association between needle reuse and lipohypertrophy. However, patients who reuse needles should not be subjected to alarming claims of excessive morbidity from this practice (A). Health care authorities and planners should be alerted to the risks associated with syringe or pen needles 6 mm or longer in children (A).
95 citations
TL;DR: Ertugliflozin 15 mg was non-inferior to glimepiride in reducing HbA1c when added to metformin in patients with T2DM and resulted in less hypoglycemia and more GMIs than glimePiride.
Abstract: This study assessed the safety and efficacy of ertugliflozin (an oral sodium-glucose cotransporter 2 inhibitor) vs. glimepiride in patients with type 2 diabetes mellitus (T2DM) inadequately controlled on metformin. This phase III, double-blind, non-inferiority study (NCT01999218) randomized patients with HbA1c ≥ 7.0% and ≤ 9.0% on stable metformin ≥ 1500 mg/day 1:1:1 to ertugliflozin 15 or 5 mg once-daily (QD), or glimepiride (titrated from 1 mg QD). The primary hypothesis was that ertugliflozin 15 mg was non-inferior to glimepiride on HbA1c (non-inferiority criterion: upper bound of the 95% confidence interval [CI] about the treatment difference < 0.3%). Mean baseline HbA1c of randomized patients (N = 1326) was 7.8%. Mean and median doses of glimepiride were 3.0 mg/day throughout the study. At week 52, the least squares mean change (95% CI) from baseline in HbA1c was − 0.6% (− 0.7, − 0.5), − 0.6% (− 0.6, − 0.5), and − 0.7% (− 0.8, − 0.7) in the ertugliflozin 15 mg, ertugliflozin 5 mg, and glimepiride groups, respectively. The between-group difference for ertugliflozin 15 mg and glimepiride of 0.1% (− 0.0, 0.2) met the pre-specified non-inferiority criterion. Relative to glimepiride, greater body weight and systolic blood pressure (SBP) reductions were observed with ertugliflozin. The overall incidence of adverse events (AEs) was similar across groups. The incidence of symptomatic hypoglycemia and genital mycotic infection (GMI) were, respectively, lower and higher with ertugliflozin relative to glimepiride. The incidences of urinary tract infection and hypovolemia AEs were not meaningfully different among the groups. Ertugliflozin 15 mg was non-inferior to glimepiride in reducing HbA1c when added to metformin in patients with T2DM. Ertugliflozin had an acceptable safety profile and resulted in less hypoglycemia and more GMIs than glimepiride. Clinicaltrials.gov NCT01999218.
84 citations
TL;DR: This review takes a practical approach to the assessment, nursing care, and medical treatment of diabetes in the elderly and highlights major challenges and suggests solutions to these commonly encountered clinical problems.
Abstract: The elderly are an important and distinct yet heterogeneous group of persons living with diabetes. The elderly have a unique biomedical, psychological, and social constitution. Their needs are different from those of younger adults. This implies that special care must be taken while evaluating and planning their nursing and management. Diabetes management in the elderly should focus on prevention and limitation of geriatric syndromes (medical conditions encountered in elderly persons), hypoglycemia (low blood glucose), and neurocognitive dysfunction (impairment in the functioning of the nervous system and brain). This review takes a practical approach to the assessment, nursing care, and medical treatment of diabetes in the elderly. It highlights major challenges and suggests solutions to these commonly encountered clinical problems.
71 citations
TL;DR: Co-initiation of ertugliflozin with sitagliptin in patients with T2DM inadequately controlled on diet and exercise provided a clinically meaningful improvement in glycemic control over 26 weeks.
Abstract: Ertugliflozin is an oral sodium-glucose cotransporter 2 inhibitor that is being developed to treat type 2 diabetes mellitus (T2DM). This study assessed the efficacy and safety of co-initiation of ertugliflozin and sitagliptin compared with placebo in patients with T2DM inadequately controlled on diet and exercise. In this phase III, randomized, double-blind, multicenter, placebo-controlled 26-week study (NCT02226003), patients with T2DM and glycated hemoglobin (HbA1c) 8.0–10.5% on diet/exercise were randomized 1:1:1 to ertugliflozin 5 mg once daily (QD) and sitagliptin 100 mg QD (E5/S100), ertugliflozin 15 mg QD and sitagliptin 100 mg QD (E15/S100), or placebo. The primary efficacy endpoint was the change from baseline in HbA1c at week 26. The mean baseline HbA1c of the randomized patients (n = 291) was 8.9%. At week 26, both ertugliflozin/sitagliptin treatments provided significant reductions from baseline in HbA1c compared with placebo [least squares mean HbA1c change (95% confidence intervals) from baseline was − 0.4% (− 0.7, − 0.2), − 1.6% (− 1.8, − 1.4), and − 1.7% (− 1.9, − 1.5) for placebo, E5/S100, and E15/S100, respectively]. At week 26, 8.3%, 35.7%, and 31.3% of patients receiving placebo, E5/S100, and E15/S100, respectively, had HbA1c < 7.0%. Significant reductions in fasting plasma glucose, 2-h post-prandial glucose, body weight, and systolic blood pressure were observed with both ertugliflozin/sitagliptin groups compared with placebo. The incidence of adverse events (AEs) was similar across the groups. The incidences of the pre-specified AEs of urinary tract infection, genital mycotic infection, symptomatic hypoglycemia, and hypovolemia were low and not meaningfully different across groups. Co-initiation of ertugliflozin with sitagliptin in patients with T2DM inadequately controlled on diet and exercise provided a clinically meaningful improvement in glycemic control over 26 weeks. Clinicaltrials.gov NCT02226003.
69 citations
TL;DR: Metformin has been shown to reduce maximal carotid intima media thickness and therefore may extend cardioprotective benefits in type 1 diabetes, and needs to be explored further in outcome trials.
Abstract: There is a rising trend of overweight and obesity among individuals with type 1 diabetes. This is often associated with insulin resistance, increased insulin dose requirements and poor glycemic control. Insulin resistance is also seen during puberty and is strongly related to increased risk of cardiovascular disease. The role of metformin as an adjunct to ongoing intensive insulin therapy in type 1 diabetics has been evaluated in several randomized trials, including the recently concluded T1D Exchange Network trial in adolescents and the REMOVAL trial in adults. Metformin reduces the insulin dose requirement, insulin-induced weight gain, and total and LDL cholesterol, but results in an increased risk of gastrointestinal adverse effects and a minor increase in the risk of hypoglycemia. In addition, metformin has been shown to reduce maximal carotid intima media thickness and therefore may extend cardioprotective benefits in type 1 diabetes. The role of metformin as adjunctive therapy in type 1 diabetes needs to be explored further in outcome trials.
61 citations
TL;DR: This review article provides a summary of relevant data regarding the use of SGLT2i medicines and focusing on specific considerations for appropriate prescribing within the T2DM management pathway, and provides a benefit/risk tool that summarises many of the aspects discussed in this review.
Abstract: Management of type 2 diabetes mellitus (T2DM) is complex and challenging, particularly for clinicians working in primary care who are faced with many competing clinical priorities. The range of available T2DM treatments has diversified significantly in recent years, generating a busy and data-rich environment in which evidence is rapidly evolving. Sodium-glucose cotransporter-2 inhibitor (SGLT2i) agents are a relatively new class of oral glucose-lowering therapy that have been available in the UK for approximately 5 years. These agents reduce the reabsorption of glucose in the kidney and increase its excretion via the urine. Conflicting messages and opinions within the clinical community have led to misconceptions concerning the efficacy, safety and appropriate position of SGLT2i therapies within the T2DM treatment pathway. To help address some of these concerns and provide advice regarding the appropriate place of these medicines in clinical practice, the Improving Diabetes Steering Committee was formed. The Committee worked together to develop this review article, providing a summary of relevant data regarding the use of SGLT2i medicines and focusing on specific considerations for appropriate prescribing within the T2DM management pathway. In addition, a benefit/risk tool has been provided (see Fig. 3) that summarises many of the aspects discussed in this review. The tool aims to support clinicians in identifying the people most likely to benefit from SGLT2i treatments, as well as situations where caution may be required. Napp Pharmaceuticals Limited.
57 citations
TL;DR: Chinese propolis is effective at improving antioxidant function in T2DM patients, partly by increasing serum antioxidant parameters.
Abstract: Propolis is a natural product with many biological activities. The present study was designed to evaluate the effects of Chinese propolis on glucose metabolism, antioxidant function, and inflammatory cytokines in patients with type 2 diabetes mellitus (T2DM). In the 18-week study, recruited T2DM patients were randomly divided into a Chinese propolis group (900 mg/day) (n = 31) and a control group (n = 30) according to fasting serum glucose levels at baseline. At the end of the study, no significant difference was found between the groups in serum glucose, glycosylated hemoglobin, insulin, aldose reductase, or adiponectin. However, serum GSH, flavonoids, and polyphenols were significantly increased, and serum lactate dehydrogenase activity was significantly reduced in the Chinese propolis group. Meanwhile, serum IL-6 was significantly increased in the Chinese propolis group. Chinese propolis is effective at improving antioxidant function in T2DM patients, partly by increasing serum antioxidant parameters.
TL;DR: Current knowledge on the epidemiology, pathogenesis, course of disease and medical management of post-liver transplantation diabetes mellitus is summarized.
Abstract: Post-liver transplantation diabetes mellitus (PLTDM) develops in up to 30% of liver transplant recipients and is associated with increased risk of mortality and multiple morbid outcomes. PLTDM is a multicausal disorder, but the main risk factor is the use of immunosuppressive agents of the calcineurin inhibitor (CNI) family (tacrolimus and cyclosporine). Additional factors, such as pre-transplant overweight, nonalcoholic steatohepatitis and hepatitis C virus infection, may further increase risk of developing PLTDM. A diagnosis of PLTDM should be established only after doses of CNI and steroids are stable and the post-operative stress has been overcome. The predominant defect induced by CNI is insulin secretory dysfunction. Plasma glucose control must start immediately after the transplant procedure in order to improve long-term results for both patient and transplant. Among the better known antidiabetics, metformin and DPP-4 inhibitors have a particularly benign profile in the PLTDM context and are the preferred oral agents for long-term management. Insulin therapy is also an effective approach that addresses the prevailing pathophysiological defect of the disorder. There is still insufficient evidence about the impact of newer families of antidiabetics (GLP-1 agonists, SGLT-2 inhibitors) on PLTDM. In this review, we summarize current knowledge on the epidemiology, pathogenesis, course of disease and medical management of PLTDM.
TL;DR: The study of real-world data from a large US EMR database suggested that among patients with T2D who initiated BI after OADs, the likelihood of reaching glycemic control diminished over time, and remained low from 12 months onwards.
Abstract: Basal insulin (BI) plays an important role in treating type 2 diabetes (T2D), especially when oral antidiabetic (OAD) medications are insufficient for glycemic control. We conducted a retrospective, observational study using electronic medical records (EMR) data from the IBM® Explorys database to evaluate the probability of achieving glycemic control over 24 months after BI initiation in patients with T2D in the USA. A cohort of 6597 patients with T2D who started BI following OAD(s) and had at least one valid glycated hemoglobin (HbA1c) result recorded both within 90 days before and 720 days after BI initiation were selected. We estimated the changes from baseline in HbA1c every 6 months, the quarterly conditional probabilities of reaching HbA1c < 7% if a patient had not achieved glycemic control prior to each quarter (Q), and the cumulative probability of reaching glycemic control over 24 months. Our cohort was representative of patients with T2D who initiated BI from OADs in the USA. The average HbA1c was 9.1% at BI initiation, and decreased robustly (1.5%) in the first 6 months after initiation with no further reductions thereafter. The conditional probability of reaching glycemic control decreased rapidly in the first year (26.6% in Q2; 17.6% in Q3; 8.6% in Q4), and then remained low (≤ 6.1%) for each quarter in the second year. Cumulatively, about 38% of patients reached HbA1c < 7% in the first year; only approximately 8% more did so in the second year. Our study of real-world data from a large US EMR database suggested that among patients with T2D who initiated BI after OADs, the likelihood of reaching glycemic control diminished over time, and remained low from 12 months onwards. Additional treatment options should be considered if patients do not reach glycemic control within 12 months of BI initiation. Sanofi Corporation.
TL;DR: The aim of the present review is to discuss the incidence and consequences of herpes zoster infection in DM and to comment on the role of vaccination against VZV in these patients.
Abstract: Accumulating evidence suggests that diabetes mellitus (DM) represents an important risk factor for both herpes zoster and post-herpetic neuralgia. Moreover, post-herpetic neuralgia appears to be more severe and persistent in diabetic patients. On the other hand, a novel vaccine against varicella-zoster virus (VZV) was recently introduced in clinical practice. Given the increased risk and severity of herpes zoster infection in patients with DM, this vaccine might be useful in this population. However, there are limited data regarding the efficacy and safety of vaccination against herpes zoster in the diabetic population. The aim of the present review is to discuss the incidence and consequences of herpes zoster infection in DM and to comment on the role of vaccination against VZV in these patients.
TL;DR: Overall urine volume returned towards baseline levels within 4 weeks of treatment with empagliflozin, consistent with a physiological, adaptive mechanism of the kidney to maintain overall body fluid balance in response to treatment initiation with a SGLT2 inhibitor.
Abstract: Empagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, ameliorates hyperglycemia in patients with type 2 diabetes (T2D) by inducing sustained glucosuria. Empagliflozin treatment was previously associated with a transient increase in 24-h urine volume in Caucasian patients with T2D, however comparable evidence in Japanese T2D individuals is scarce. We therefore assessed acute and chronic changes in 24-h urine volume and fluid intake with empagliflozin in Japanese patients with T2D. In this randomized, double-blind, placebo-controlled, parallel-group, multiple-dose, 4-week trial, 100 Japanese patients with T2D were randomized to receive either 1, 5, 10, or 25 mg empagliflozin or placebo once-daily. Changes from baseline in 24-h urine volume and fluid intake were assessed at days 1, 27, and 28 after the initiation of empagliflozin. The 24-h urine volume and fluid intake were comparable across all treatment groups at baseline. Patients treated with either 10 or 25 mg empagliflozin (i.e., the licensed doses in Japan) showed a significant increase in 24-h urine volume compared to placebo at day 1 (mean change from baseline: + 0.83, + 1.08, and + 0.29 L/day in the empagliflozin 10 and 25 mg groups and the placebo group, respectively; both p 0.05). The 24-h fluid intake was comparable across all study groups throughout the entire study period. No events consistent with dehydration were reported during empagliflozin treatment. Treatment initiation with empagliflozin in Japanese patients with T2D was associated with transient diuresis; however, overall urine volume returned towards baseline levels within 4 weeks of treatment. These findings are consistent with a physiological, adaptive mechanism of the kidney to maintain overall body fluid balance in response to treatment initiation with a SGLT2 inhibitor. NCT00885118. Nippon Boehringer Ingelheim Co., Ltd.
TL;DR: The editorial highlights the need to focus on symptomatic well-being in diabetes, along with efforts to achieve numerical targets, as well as proposed condition ‘diabetes fatigue syndrome’ (DFS), which is commonly encountered in clinical practice.
Abstract: In this editorial we propose a condition that we refer to as ‘diabetes fatigue syndrome’ (DFS), which is commonly encountered in clinical practice. We define DFS as a multifactorial syndrome of fatigue or easy fatigability that occurs in persons with diabetes. It may be caused by a variety of lifestyle, nutritional, medical, psychological, glycemia/diabetes-related, and endocrine and iatrogenic factors. The authors share clinical pearls which can help the diabetes healthcare provider diagnose DFS, identify its etiologic factors and manage the syndrome. The editorial highlights the need to focus on symptomatic well-being in diabetes, along with efforts to achieve numerical targets.
TL;DR: The rationale, advantages, disadvantages, and implementation of currently available strategies for basal insulin treatment intensification in patients with T2D are discussed.
Abstract: As the number of people living with type 2 diabetes (T2D) continues to rise, managing their complex needs presents an increasing challenge to physicians. While treatment guidelines provide evidence-based guidance, they are not prescriptive—rather they emphasize individualization of management based on a patient’s clinical needs and preferences. Physicians, therefore, need to be fully aware of the advantages and disadvantages of the multiple and increasing treatment options available to them at each stage of the disease. The progressive nature of T2D means that treatment with basal insulin will become inevitable for many patients, while for some patients basal insulin alone will eventually be insufficient for maintaining glycemic targets. Recent guidelines recommend two basic approaches for intensifying basal insulin: the use of rapid-acting insulin, either as additional prandial injections or as part of premix (biphasic) insulin; and the addition of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) to the insulin therapy, which can be administered via subcutaneous injection once or twice daily, or weekly depending on formulation. More recently, two fixed-ratio combinations of basal insulin and a GLP-1 RA that allow for once-daily dosing have been approved. Each of these approaches has potential benefits and drawbacks, particularly in terms of risk for hypoglycemia, weight change, convenience, and side effects. Understanding these differences is central to guiding patient and physician choice. This article discusses the rationale, advantages, disadvantages, and implementation of currently available strategies for basal insulin treatment intensification in patients with T2D. Funding: Sanofi US, Inc.
TL;DR: The combination of a GLP-1 agonist and an SGLT2-inhibitor has additive effects on lowering HbA1c and systolic blood pressure, body weight and cardiac risk and has the potential to synergistically reduce cardiovascular events and decelerate renal decompensation.
Abstract: When treating type 2 diabetes, drugs that cause hypoglycemia and weight gain should, if possible, be avoided. In addition, due to the increased incidence and prevalence of cardiovascular disease, cardiac events and heart failure, as well as the accelerated renal decompensation that may occur with type 2 diabetes, hypoglycemic agents that have the potential to lower cardiac and renal risk should be utilized as early as possible in the course of the disease. This is a literature review of the efficacy of combined treatment with a glucagon-like peptide 1 (GLP-1) agonist and a sodium glucose cotransporter-2 (SGLT2) inhibitor in lowering glycated hemoglobin (HbA1c) level, cardiac risk, cardiac events and renal decompensation. Evidence is presented which shows that the efficacy of combined SGLT2 inhibitor/GLP-1 receptor agonist therapy is additive in lowering HbA1c level, systolic blood pressure and body weight. This combined therapy also has the potential to cause further reductions in major cardiovascular events and renal decompensation than those achieved with either drug used as monotherapy or in combination with other hypoglycemic agents. The combination of a GLP-1 agonist and an SGLT2-inhibitor has additive effects on lowering HbA1c and systolic blood pressure, body weight and cardiac risk and has the potential to synergistically reduce cardiovascular events and decelerate renal decompensation. A large prospective study of this combination is needed to prove that this synergism, especially as it applies to cardiac risk factors, cardiac events and mortality and preservation of renal function, is proven.
TL;DR: The evidence indicates that these drugs are highly effective and safe in the elderly and in the presence of mild, moderate and severe renal failure improving glycemic control with low risk of hypoglycemia.
Abstract: The safety and efficacy of dipeptidyl peptidase-4 (DPP4) inhibitors as monotherapy or in combination with other oral antidiabetic agents or basal insulin are well established. DPP4 inhibitors stimulate glucose-dependent insulin secretion and inhibit glucagon production. As monotherapy, they reduce the hemoglobin A1c level by about 0.6–0.8%. The addition of a DPP4 inhibitor to basal insulin is an attractive option, because they lower both postprandial and fasting plasma glucose concentrations without increasing the risk of hypoglycemia or weight gain. The present review summarizes the extensive evidence on the combination therapy of DPP4 inhibitors and insulin-based regimens in patients with type 2 diabetes. We focus our discussion on challenging clinical scenarios including patients with chronic renal impairment, elderly persons and hospitalized patients. The evidence indicates that these drugs are highly effective and safe in the elderly and in the presence of mild, moderate and severe renal failure improving glycemic control with low risk of hypoglycemia. In addition, several randomized-controlled trials have shown that the use of DPP4 inhibitors in combination with basal insulin represents an alternative to the basal-bolus insulin regimen in hospitalized patients with type 2 diabetes.
TL;DR: Prenatal exposure to metformin is associated with increased offspring weight, but not with height or BMI, and smaller follow-up studies are needed to confirm and look into the implications of these findings.
Abstract: Antidiabetic drugs (OADs) are increasingly prescribed to treat hyperglycaemia during pregnancy in women with gestational diabetes mellitus (GDM) or polycystic ovary syndrome (PCOS), even though long-term effects on offspring are unknown. This systematic review summarises the evidence of follow-up studies of randomised controlled trials (RCTs) reporting on long-term effects of prenatal exposure to OADs on offspring. The MEDLINE, EMBASE and CENTRAL databases were searched from inception to April 2018 for the concepts antidiabetic agents and prenatal exposure (or pregnancy and offspring/child) in combination with an RCT search filter. RCTs evaluating post-neonatal health effects in offspring and comparing maternal treatment with an OAD with no treatment, placebo, an alternative OAD or insulin during pregnancy were eligible for inclusion. Two independent researchers selected, extracted and assessed the data. Meta-analyses were performed using a random effects model and the Cochrane Collaboration’s risk of bias tool was used for quality assessment. Ten studies were included, with a maximal follow-up duration of 9 years, comprising 778 children of mothers with GDM or PCOS who were randomised to either metformin or insulin/placebo during pregnancy. Meta-analysis showed that children prenatally exposed to metformin were heavier compared to controls (standardised mean difference (SMD) 0.26 [95% CI 0.11–0.41]), but not taller (SMD 0.10 [95% CI −0.14–0.33]). Additionally, offspring body mass index (BMI) z scores did not differ according to metformin exposure (mean difference 0.30 [95% CI −0.01–0.61]). Individual small studies reported that prenatal exposure to metformin was associated with greater mid-upper arm, head and waist circumferences, biceps skinfolds, waist-to-height ratio, more arm fat, higher fasting glucose, ferritin and lower LDL cholesterol in offspring. Prenatal exposure to metformin is associated with increased offspring weight, but not with height or BMI. Larger follow-up studies are needed to confirm and look into the implications of these findings. Plain language summary available for this article.
TL;DR: Overall, once-weekly semaglutide 1.0 mg as an add-on to 1–2 OADs is the most efficacious GLP-1 RA in terms of the reduction of HbA1c and weight from baseline after 6 months of treatment.
Abstract: Once-weekly semaglutide is a new glucagon-like peptide-1 (GLP-1) analogue administered at a 1.0 or 0.5 mg dose. As head-to-head trials assessing once-weekly semaglutide as an add-on to 1–2 oral anti-diabetic drugs (OADs) vs other GLP-1 receptor agonists (GLP-1 RAs) are limited, a network meta-analysis (NMA) was performed. The objective was to assess the relative efficacy and safety of once-weekly semaglutide vs GLP-1 RAs in patients with type 2 diabetes (T2D) inadequately controlled on 1–2 OADs. A systematic literature review (SLR) was conducted in order to identify trials of GLP-1 RAs in patients inadequately controlled on 1–2 OADs. Data at 24 ± 4 weeks were extracted for efficacy and safety outcomes (feasible for analysis in a NMA), which included the key outcomes of change from baseline in glycated hemoglobin (HbA1c), systolic blood pressure (SBP), and weight, as well as discontinuation due to adverse events (AEs). Data were synthesized using a NMA and a Bayesian framework. In total, 26 studies were included across the base case analyses. Once-weekly semaglutide 1.0 mg was associated with significantly greater reductions in HbA1c and weight vs all GLP-1 RA comparators. Once-weekly semaglutide 0.5 mg also achieved significantly greater reductions in HbA1c and weight compared with the majority of other GLP-1 RAs. Both doses of once-weekly semaglutide were associated with similar odds of discontinuation due to AEs compared with other GLP-1 RAs. Overall, once-weekly semaglutide 1.0 mg as an add-on to 1–2 OADs is the most efficacious GLP-1 RA in terms of the reduction of HbA1c and weight from baseline after 6 months of treatment. In addition, the analysis suggests that once-weekly semaglutide is well tolerated and not associated with an increase in discontinuations due to AEs compared with other GLP-1 RAs. Novo Nordisk.
TL;DR: Time-to-event analyses that account for missing data inherent to a non-interventional study design demonstrated that participants receiving ≥ 7 in injections in the first year had a faster response, but the duration of the response was shorter compared to the subgroups receiving 1–3 and 4–6 injections.
Abstract: The prospective, non-interventional OCEAN study examined the use of intravitreal ranibizumab injections for the treatment of diabetic macular oedema (DME) in a real-world setting in Germany. Adults with DME receiving ≥ 1 ranibizumab (0.5 mg) injections were recruited by 250 ophthalmologists. Best-corrected visual acuity (VA) testing, imaging and treatments were performed according to the investigators’ routine practice and documented over 24 months. The full analysis set included 1226 participants. Mean baseline VA was 60.6 [95% CI: 59.7; 61.5] Early Treatment Diabetic Retinopathy Study letters. VA improved by ≥ 15 letters in 21.5% and 23.5% of the participants at 12 months and 24 months, respectively. They received a mean number of 4.42 [95% CI: 4.30; 4.54] injections in the first year and 5.52 [95% CI: 5.32; 5.73] injections over 24 months, which was markedly lower than in clinical trials. Only 33.4% of the participants received an upload with four initial monthly injections as recommended by the German ophthalmologic societies. Time-to-event analyses that account for missing data inherent to a non-interventional study design demonstrated that participants receiving ≥ 7 injections in the first year had a faster response, but the duration of the response was shorter compared to the subgroups receiving 1–3 and 4–6 injections. Serious adverse events were reported for 143/1250 (11.4%) participants in the safety population. Under-treatment is a major problem of DME anti- vascular endothelial growth factor therapy under real life conditions. Despite fewer injections given compared to randomised controlled trials with a consequently reduced overall mean visual gain, a profound functional improvement (≥ 15 letters) was achieved over 2 years in 23.5% of eyes with DME. NCT02194803, ClinicalTrials.gov. Novartis Pharma GmbH, Nuremberg, Germany.
TL;DR: Current evidence on the long-term safety risks associated with SU therapy relative to other oral glucose-lowering therapies is summarized and the methodological rigor of such studies is questionable.
Abstract: Among the most pressing clinical decisions in type 2 diabetes treatments are which drugs should be used after metformin is no longer sufficient, and whether sulfonylureas (SUs) should remain as a suitable second-line treatment. In this article we summarize current evidence on the long-term safety risks associated with SU therapy relative to other oral glucose-lowering therapies. The MEDLINE database and Clinicaltrials.gov were searched for observational and experimental studies comparing the safety of SUs to that of other diabetes medications in people with type 2 diabetes mellitus through December 15, 2015. Studies with at least 1 year of follow-up, which explicitly examined major cardiovascular events or death in patients who showed no evidence of serious conditions at baseline, were selected for inclusion in meta-analyses. SU treatment was associated with an elevated risk relative to treatment with metformin (METF), thiazolidinedione (TZD), dipeptidyl peptidase-4 inhibitor (DPP-4), and glucagon-like peptide-1 (GLP-1) agonist classes, either when compared alone (as a monotherapy) or when used in combination with METF. Significant findings were almost entirely derived from nontrial data and not confirmed by smaller, efficacy designed randomized controlled trials whose effects were in the same direction but much more imprecise. Although much of the evidence is derived and will continue to come from observational studies, the methodological rigor of such studies is questionable. A key challenge for evaluators is the extent to which they should incorporate evidence from study designs that are quasi-experimental.
TL;DR: This real-world analysis suggests differences exist in persistence between patients treated with various GLP-1 RAs, and patients prescribed exBID recorded the lowest and those prescribed DULA the highest persistence with therapy.
Abstract: Real-world evidence on glucagon-like peptide-1 receptor agonist (GLP-1 RAs) usage is emerging in different European countries but is lacking in Italy. This retrospective cohort study aimed to describe the real-world drug utilization patterns in patients initiating GLP-1 RAs for treating T2DM in Italy. Adults aged ≥ 20 years and with ≥ 1 oral antidiabetic drug (alone or in combination with insulin) other than GLP-1 RAs in the 6 months prior to initiating exenatide twice daily (exBID), exenatide once weekly (exQW), dulaglutide once weekly (DULA), liraglutide once daily (LIRA) or lixisenatide once daily (LIXI) between March and July 2016 were retrospectively identified in the Italian IMS LifeLink™ longitudinal prescriptions database (retail pharmacy data). Patients with ≥ 6-month follow-up (defined as evidence of any prescription activity) were included. Proportions of patients who remained persistent (continued treatment until discontinuation/switch) in the first 6 months and of those who discontinued or switched to a different GLP-1 RA over the entire follow-up were recorded. For each treatment, the average daily/weekly dosage (ADD/AWD) while persistent during the available follow-up was calculated. We identified 7319 patients: 92 exBID, 970 exQW, 3368 DULA, 2573 LIRA and 316 LIXI. Across treatments, 89% patients were ≥ 50 years old, 54% were males, and the median follow-up duration ranged between 8.1 and 8.7 months. At 6 months, 35% exBID, 47% exQW, 62% DULA, 50% LIRA and 40% LIXI patients remained persistent. Over the entire follow-up, median persistence days varied from 73 (exBID) to > 300 days (DULA). The mean ± SD ADD/AWD was exBID: 17.7 ± 2.1 µg/day; exQW: 2.1 ± 0.1 mg/week; DULA: 1.5 ± 0.2 mg/week; LIRA: 1.5 ± 0.2 mg/day; LIXI: 21.0 ± 5.5 µg/day. This real-world analysis suggests differences exist in persistence between patients treated with various GLP-1 RAs. Among the investigated treatments, patients prescribed exBID recorded the lowest and those prescribed DULA the highest persistence with therapy. Eli Lilly and Co., Indianapolis, IN, USA.
TL;DR: Artificial pancreas might be considered an effective and safe alternative to be used during a 24-h basis in patients with T1DM.
Abstract: Insulin injection is the main treatment in patients with type 1 diabetes mellitus (T1DM). Even though continuous glucose monitoring has significantly improved the conditions of these patients, limitations still exist. To further enhance glucose control in patients with T1DM, an artificial pancreas has been developed. We aimed to systematically compare artificial pancreas with its control group during a 24-h basis in patients with T1DM. Electronic databases were carefully searched for English publications comparing artificial pancreas with its control group. Overall daytime and nighttime glucose parameters were considered as the endpoints. Data were evaluated by means of weighted mean differences (WMDs) and 95% confidence intervals (CIs) generated by RevMan 5.3 software. A total number of 354 patients were included. Artificial pancreas significantly maintained a better mean concentration of glucose (WMD − 1.03, 95% CI − 1.32 to − 0.75; P = 0.00001). Time spent in the hypoglycemic phase was also significantly lower (WMD − 1.23, 95% CI − 1.56 to − 0.91; P = 0.00001). Daily insulin requirement also significantly favored artificial pancreas (WMD − 3.43, 95% CI − 4.27 to − 2.59; P = 0.00001). Time spent outside the euglycemic phase and hyperglycemia phase (glucose > 10.0 mmol/L) also significantly favored artificial pancreas. Also, the numbers of hypoglycemic events were not significantly different. Artificial pancreas might be considered an effective and safe alternative to be used during a 24-h basis in patients with T1DM.
TL;DR: Evaluating the efficacy and safety of initial combination therapy compared with monotherapy in drug-naïve type 2 diabetes patients found initial combination therapies with metformin plus another anti-diabetes drug showed significant reductions in HbA1c and a similar risk of hypoglycemia.
Abstract: Introduction
The aim of this study was to evaluate the efficacy and safety of initial combination therapy compared with monotherapy in drug-naive type 2 diabetes patients
TL;DR: The findings suggest that diabetes management programs must explicitly address concordant, discordant, and dominant conditions because patients may have distinctly different health care needs and utilization patterns depending on their comorbidity profiles.
Abstract: Previous studies suggest that the type and combination of comorbidities may impact diabetes care, but their cost implications are less clear. This study characterized how diabetes patients’ health care utilization and costs may vary according to comorbidity type classified on the basis of the Piette and Kerr framework. We conducted a retrospective observational study of privately insured US adults newly diagnosed with type 2 diabetes (n = 138,466) using the 2014–2016 Optum Clinformatics® Data Mart. Diabetes patients were classified into five mutually exclusive comorbidity groups: concordant only, discordant only, both concordant and discordant, any dominant, and none. We estimated average health care costs of each comorbidity group by using generalized linear models, adjusting for patient demographics, region, insurance type, and prior-year costs. Most type 2 diabetes patients had discordant conditions only (27%), dominant conditions (25%), or both concordant and discordant conditions (24%); 7% had concordant conditions only. In adjusted analyses, comorbidities were significantly associated with higher health care costs (p < 0.0001) and the magnitude of the association varied with comorbidity type. Diabetes patients with dominant comorbidities incurred substantially higher costs ($38,168) compared with individuals with both concordant and discordant conditions ($20,401), discordant conditions only ($9173), concordant conditions only ($9000), and no comorbidities ($3365). More than half of the total costs in our sample (53%) were attributable to 25% of diabetes patients who had dominant comorbidities. Diabetes patients with both concordant and discordant conditions and with clinically dominant conditions incurred substantially higher health costs than other diabetes patients. Our findings suggest that diabetes management programs must explicitly address concordant, discordant, and dominant conditions because patients may have distinctly different health care needs and utilization patterns depending on their comorbidity profiles. The Piette and Kerr framework may serve as a screening tool to identify high-need, high-cost diabetes patients and suggest targets for tailored interventions. Sanofi.
TL;DR: Trust in physician is associated with an increased adherence and with decreased diabetes-related distress, and this distress was also associated with poor adherence in this study.
Abstract: Type 2 diabetes represents a significant public health issue, with increasing prevalence in developing countries while adherence to insulin treatment remains a challenge. No studies have evaluated the relationship between adherence to insulin, diabetes-related distress, and trust in physician among persons with diabetes. Our objectives were to evaluate treatment adherence to insulin, emotional distress (using the Problem Areas in Diabetes Questionnaire, PAID), trust in physician, and to examine associations between them among Lebanese patients with diabetes. This cross-sectional study, conducted in all districts of Lebanon between August 2016 and April 2017, enrolled 135 adult patients. The mean percentage score of adherence to insulin was 79.7 ± 19.94. A significantly higher mean adherence score was found in non-sedentary (81.96) compared to sedentary patients (67.41) (p = 0.017), with no difference between gender, employment, rural vs non-rural residence, or familial history of diabetes. In addition, no significant relationship was seen between adherence score and education level, smoking, or alcohol intake. A significant positive association was found between trust in physician and adherence scores, whereas a significant but negative one was found between PAID and adherence scores. The results of linear regressions showed that a secondary level of education (beta = − 13.48) significantly decreased the trust in physician score, whereas the total number of oral antidiabetics (beta = 0.93) increased it. Having a sedentary lifestyle (beta = − 12.73) and smoking < 3 waterpipes/week compared to no smoking (beta = − 16.82) significantly decreased the adherence score. Female gender (beta = 10.46), smoking < 3 waterpipes (beta = 27.42) and 3 + waterpipes/week (beta = 17.95) significantly increased the PAID score. Trust in physician is associated with an increased adherence and with decreased diabetes-related distress. This distress was also associated with poor adherence in our study.
TL;DR: The amelioration of hepatic dysfunction was mediated partly through an alleviation of hyperglycemia and possibly through an improvement in insulin resistance, independent of BW.
Abstract: Sodium–glucose co-transporter 2 inhibitors (SGLT2i) improve hepatic dysfunction, although studies focusing on their underlying mechanisms are lacking, especially ones on dapagliflozin and empagliflozin. Here, we investigated the relationship between amelioration of hepatic dysfunction and improvement in various metabolic parameters among Chinese subjects with type 2 diabetes (T2DM). This was a single-center, retrospective, observational study that involved 115 Chinese participants with T2DM treated with either dapagliflozin or empagliflozin for at least 6 months between July 2016 and February 2017. Of the 115 participants included in this study, 69 received dapagliflozin and 46 received empagliflozin. After 6 months of treatment, all patients showed significant improvements in body weight (BW), systolic blood pressure (SBP) and fasting glucose (FG) and glycated hemoglobin (HbA1c) levels. All participants also showed a significant reduction in serum alanine aminotransferase (ALT) levels, from 40.3 ± 28.0 to 29.0 ± 14.1 U/L (p < 0.001). Pearson’s correlation analysis revealed a positive correlation between the reduction in ALT levels after treatment with the respective SGLT2i and changes in FG (p = 0.014) and HbA1c (p = 0.043) levels over 6 months, but not with changes in BW and SBP. Multiple linear regression analysis revealed that the reduction in serum ALT levels was independently associated with changes in both HbA1c and FG but not with the changes in the other clinical variables, including BW. Dapagliflozin and empagliflozin improved both metabolic and hepatic dysfunction as a class effect. The amelioration of hepatic dysfunction was mediated partly through an alleviation of hyperglycemia and possibly through an improvement in insulin resistance, independent of BW.
TL;DR: There have been parallel increases in the rate of admissions due to dysglycaemia and the rate to prescriptions of antidiabetic medications in England and Wales between 1999 and 2016.
Abstract: Hypoglycaemia and hyperglycaemia are common adverse events associated with antidiabetic medications. They are also a common cause of hospital admissions for people with diabetes. The objective of the study was to explore the trends in hospital admissions due to hypoglycaemia and hyperglycaemia and in the prescriptions of antidiabetic medications in England and Wales. We conducted an observational study during the period 1999–2016. Hospital admission data for patients from all age groups were extracted from the Hospital Episode Statistics database in England and the Patient Episode Database for Wales. Data on prescriptions of antidiabetic medications were extracted from the Prescription Cost Analysis database from 2004 to 2016. Between 1999 and 2016, the hospital admission rate increased by 173.0% [from 17.2 (95% CI 16.9–17.6) to 47.1 (95% CI 46.5–47.6) per 100,000 persons] for hypoglycaemia and by 147.0% [from 22.8 (95% CI 22.4–23.2) to 56.3 (95% CI 55.7–56.9) per 100,000 persons] for hyperglycaemia. The prescription rate for all antidiabetic medications increased between 2004 and 2016 by 116.0% [from 373.0 (95% CI 373.0–373.0) to 806.0 (95% CI 806.0–806.0) prescriptions per 1000 persons]. There was a parallel increase in the rate of antidiabetic medication prescriptions during the same study period, with correlation coefficients of 0.94 for hypoglycaemia and 0.98 for hyperglycaemia, respectively. There have been parallel increases in the rate of admissions due to dysglycaemia and the rate of antidiabetic prescriptions in England and Wales. Further analytical studies are required to investigate whether increased admission for dysglycaemia is associated with increased use of antidiabetic medications.