Showing papers in "Diabetes Care in 2014"
TL;DR: DCCT/EDIC has demonstrated the effectiveness of intensive therapy in reducing the long-term complications of T1DM and improving the prospects for a healthy life span and the durability of the DCCT effects on the more-advanced stages of diabetes complications including cardiovascular disease.
Abstract: OBJECTIVE The Diabetes Control and Complications Trial (DCCT) was designed to test the glucose hypothesis and determine whether the complications of type 1 diabetes (T1DM) could be prevented or delayed. The Epidemiology of Diabetes Interventions and Complications (EDIC) observational follow-up determined the durability of the DCCT effects on the more-advanced stages of diabetes complications including cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS The DCCT (1982-1993) was a controlled clinical trial in 1,441 subjects with T1DM comparing intensive therapy (INT), aimed at achieving levels of glycemia as close to the nondiabetic range as safely possible, with conventional therapy (CON), which aimed to maintain safe asymptomatic glucose control. INT utilized three or more daily insulin injections or insulin pump therapy guided by self-monitored glucose. EDIC (1994-present) is an observational study of the DCCT cohort. RESULTS The DCCT followed >99% of the cohort for a mean of 6.5 years and demonstrated a 35-76% reduction in the early stages of microvascular disease with INT, with a median HbA1c of 7%, compared with CONV, with a median HbA1c of 9%. The major adverse effect of INT was a threefold increased risk of hypoglycemia, which was not associated with a decline in cognitive function or quality of life. EDIC showed a durable effect of initial assigned therapies despite a loss of the glycemic separation (metabolic memory) and demonstrated that the reduction in early-stage complications during the DCCT translated into substantial reductions in severe complications and CVD. CONCLUSIONS DCCT/EDIC has demonstrated the effectiveness of INT in reducing the long-term complications of T1DM and improving the prospects for a healthy life span.
1,353 citations
TL;DR: The ADA also recognizes the integral role of nutrition therapy in overall diabetes management and has historically recommended that each person with diabetes be actively engaged in self-management, education, and treatment planning with his or her health care provider, which includes the collaborative development of an individualized eating plan as mentioned in this paper.
Abstract: A healthful eating pattern, regular physical activity, and often pharmacotherapy are key components of diabetes management. For many individuals with diabetes, the most challenging part of the treatment plan is determining what to eat. It is the position of the American Diabetes Association (ADA) that there is not a “one-size-fits-all” eating pattern for individuals with diabetes. The ADA also recognizes the integral role of nutrition therapy in overall diabetes management and has historically recommended that each person with diabetes be actively engaged in self-management, education, and treatment planning with his or her health care provider, which includes the collaborative development of an individualized eating plan (1,2). Therefore, it is important that all members of the health care team be knowledgeable about diabetes nutrition therapy and support its implementation.
This position statement on nutrition therapy for individuals living with diabetes replaces previous position statements, the last of which was published in 2008 (3). Unless otherwise noted, research reviewed was limited to those studies conducted in adults diagnosed with type 1 or type 2 diabetes. Nutrition therapy for the prevention of type 2 diabetes and for the management of diabetes complications and gestational diabetes mellitus is not addressed in this review.
A grading system, developed by the ADA and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations (1) (Table 1). The level of evidence that supports each recommendation is listed after the recommendation using the letters A, B, C, or E. A table linking recommendations to evidence can be reviewed at http://professional.diabetes.org/nutrition. Members of the Nutrition Recommendations Writing Group Committee disclosed all potential financial conflicts of interest with industry. These disclosures were discussed at the onset of the position statement development process. Members of this committee, their employers, …
941 citations
TL;DR: This position statement summarizes available data specific to the comprehensive care of individuals with type 1 diabetes to enhance the ability to recognize and manage this disease, to prevent its associated complications, and to eventually cure and prevent this disease.
Abstract: Type 1 diabetes is characterized by an immune-mediated depletion of β-cells that results in lifelong dependence on exogenous insulin. While both type 1 and type 2 diabetes result in hyperglycemia, the pathophysiology and etiology of the diseases are distinct and require us to consider each type of diabetes independently. As such, this position statement summarizes available data specific to the comprehensive care of individuals with type 1 diabetes. The goal is to enhance our ability to recognize and manage type 1 diabetes, to prevent its associated complications, and to eventually cure and prevent this disease.
The exact number of individuals with type 1 diabetes around the world is not known, but in the U.S., there are estimated to be up to 3 million (1). Although it has long been called “juvenile diabetes” due to the more frequent and relatively straightforward diagnosis in children, the majority of individuals with type 1 diabetes are adults.
Most children are referred and treated in tertiary centers, where clinical data are more readily captured. The SEARCH for Diabetes in Youth study estimated that, in 2009, 18,436 U.S. youth were newly diagnosed with type 1 diabetes (12,945 non-Hispanic white, 3,098 Hispanic, 2,070 non-Hispanic black, 276 Asian-Pacific Islander, and 47 American Indian) (2). Worldwide, ∼78,000 youth are diagnosed with type 1 diabetes annually. Incidence varies tremendously among countries: East Asians and American Indians have the lowest incidence rates (0.1–8 per 100,000/year) as compared with the Finnish who have the highest rates (>64.2 per 100,000/year) (3). In the U.S., the number of youth with type 1 diabetes was estimated to be 166,984 (4).
The precise incidence of new-onset type 1 diabetes in those over 20 years of age is unknown. This may be due to the prolonged phase of onset and the subtleties in distinguishing the different …
729 citations
TL;DR: The National Standards for Diabetes Self-Management Education are designed to define quality DSME and support and to assist diabetes educators in providing evidence-based education and self-management support and serve as a guide for nonaccredited and nonrecognized providers and programs.
Abstract: By the most recent estimates, 18.8 million people in the U.S. have been diagnosed with diabetes and an additional 7 million are believed to be living with undiagnosed diabetes. At the same time, 79 million people are estimated to have blood glucose levels in the range of prediabetes or categories of increased risk for diabetes. Thus, more than 100 million Americans are at risk for developing the devastating complications of diabetes (1).
Diabetes self-management education (DSME) is a critical element of care for all people with diabetes and those at risk for developing the disease. It is necessary in order to prevent or delay the complications of diabetes (2–6) and has elements related to lifestyle changes that are also essential for individuals with prediabetes as part of efforts to prevent the disease (7,8). The National Standards for Diabetes Self-Management Education are designed to define quality DSME and support and to assist diabetes educators in providing evidence-based education and self-management support. The Standards are applicable to educators in solo practice as well as those in large multicenter programs—and everyone in between. There are many good models for the provision of diabetes education and support. The Standards do not endorse any one approach, but rather seek to delineate the commonalities among effective and excellent self-management education strategies. These are the standards used in the field for recognition and accreditation. They also serve as a guide for nonaccredited and nonrecognized providers and programs.
Because of the dynamic nature of health care and diabetes-related research, the Standards are reviewed and revised approximately every 5 years by key stakeholders and experts within the diabetes education community. In the fall of 2011, a Task Force was jointly convened by the American Association of Diabetes Educators (AADE) and the American Diabetes Association …
575 citations
Colorado School of Public Health1, Wake Forest University2, Cincinnati Children's Hospital Medical Center3, Centers for Disease Control and Prevention4, Kaiser Permanente5, National Institutes of Health6, University of Washington7, University of North Carolina at Chapel Hill8, University of Hawaii at Manoa9, Monterrey Institute of Technology and Higher Education10
TL;DR: Markers of micro- and macrovascular complications are evident in youth with either type 1 and type 2 diabetes, highlighting the seriousness of diabetes in this contemporary cohort of youth.
Abstract: The SEARCH for Diabetes in Youth (SEARCH) study was initiated in 2000, with funding from the Centers for Disease Control and Prevention and support from the National Institute of Diabetes and Digestive and Kidney Diseases, to address major knowledge gaps in the understanding of childhood diabetes. SEARCH is being conducted at five sites across the U.S. and represents the largest, most diverse study of diabetes among U.S. youth. An active registry of youth diagnosed with diabetes at age <20 years allows the assessment of prevalence (in 2001 and 2009), annual incidence (since 2002), and trends by age, race/ethnicity, sex, and diabetes type. Prevalence increased significantly from 2001 to 2009 for both type 1 and type 2 diabetes in most age, sex, and race/ethnic groups. SEARCH has also established a longitudinal cohort to assess the natural history and risk factors for acute and chronic diabetes-related complications as well as the quality of care and quality of life of persons with diabetes from diagnosis into young adulthood. Many youth with diabetes, particularly those from low-resourced racial/ethnic minority populations, are not meeting recommended guidelines for diabetes care. Markers of micro- and macrovascular complications are evident in youth with either diabetes type, highlighting the seriousness of diabetes in this contemporary cohort. This review summarizes the study methods, describes key registry and cohort findings and their clinical and public health implications, and discusses future directions.
540 citations
TL;DR: This current state summary and research recommendations are designed to guide advances in care and the generation of new knowledge that will meaningfully improve life for people with DKD.
Abstract: The incidence and prevalence of diabetes mellitus have grown significantly throughout the world, due primarily to the increase in type 2 diabetes. This overall increase in the number of people with diabetes has had a major impact on development of diabetic kidney disease (DKD), one of the most frequent complications of both types of diabetes. DKD is the leading cause of end-stage renal disease (ESRD), accounting for approximately 50% of cases in the developed world. Although incidence rates for ESRD attributable to DKD have recently stabilized, these rates continue to rise in high-risk groups such as middle-aged African Americans, Native Americans, and Hispanics. The costs of care for people with DKD are extraordinarily high. In the Medicare population alone, DKD-related expenditures among this mostly older group were nearly $25 billion in 2011. Due to the high human and societal costs, the Consensus Conference on Chronic Kidney Disease and Diabetes was convened by the American Diabetes Association in collaboration with the American Society of Nephrology and the National Kidney Foundation to appraise issues regarding patient management, highlighting current practices and new directions. Major topic areas in DKD included 1) identification and monitoring, 2) cardiovascular disease and management of dyslipidemia, 3) hypertension and use of renin-angiotensin-aldosterone system blockade and mineralocorticoid receptor blockade, 4) glycemia measurement, hypoglycemia, and drug therapies, 5) nutrition and general care in advanced-stage chronic kidney disease, 6) children and adolescents, and 7) multidisciplinary approaches and medical home models for health care delivery. This current state summary and research recommendations are designed to guide advances in care and the generation of new knowledge that will meaningfully improve life for people with DKD.
478 citations
TL;DR: Evidence suggests that pragmatic diabetes prevention programs are effective and can be improved by maximizing guideline adherence, but more research is needed to establish optimal strategies for maximizing both cost-effectiveness and longer-term maintenance of weight loss and diabetes prevention effects.
Abstract: OBJECTIVE To summarize the evidence on effectiveness of translational diabetes prevention programs, based on promoting lifestyle change to prevent type 2 diabetes in real-world settings and to examine whether adherence to international guideline recommendations is associated with effectiveness. RESEARCH DESIGN AND METHODS Bibliographic databases were searched up to July 2012. Included studies had a follow-up of ≥12 months and outcomes comparing change in body composition, glycemic control, or progression to diabetes. Lifestyle interventions aimed to translate evidence from previous efficacy trials of diabetes prevention into real-world intervention programs. Data were combined using random-effects meta-analysis and meta-regression considering the relationship between intervention effectiveness and adherence to guidelines. RESULTS Twenty-five studies met the inclusion criteria. The primary meta-analysis included 22 studies (24 study groups) with outcome data for weight loss at 12 months. The pooled result of the direct pairwise meta-analysis shows that lifestyle interventions resulted in a mean weight loss of 2.12 kg (95% CI -2.61 to -1.63; I(2) = 91.4%). Adherence to guidelines was significantly associated with a greater weight loss (an increase of 0.3 kg per point increase on a 12-point guideline-adherence scale). CONCLUSIONS Evidence suggests that pragmatic diabetes prevention programs are effective. Effectiveness varies substantially between programs but can be improved by maximizing guideline adherence. However, more research is needed to establish optimal strategies for maximizing both cost-effectiveness and longer-term maintenance of weight loss and diabetes prevention effects.
453 citations
TL;DR: The foundation of β-cell failure in type 2 diabetes (T2D) is examined and areas for future research on the underlying mechanisms that may lead to improved prevention and treatment are suggested.
Abstract: OBJECTIVE This article examines the foundation of β-cell failure in type 2 diabetes (T2D) and suggests areas for future research on the underlying mechanisms that may lead to improved prevention and treatment. RESEARCH DESIGN AND METHODS A group of experts participated in a conference on 14–16 October 2013 cosponsored by the Endocrine Society and the American Diabetes Association. A writing group prepared this summary and recommendations. RESULTS The writing group based this article on conference presentations, discussion, and debate. Topics covered include genetic predisposition, foundations of β-cell failure, natural history of β-cell failure, and impact of therapeutic interventions. CONCLUSIONS β-Cell failure is central to the development and progression of T2D. It antedates and predicts diabetes onset and progression, is in part genetically determined, and often can be identified with accuracy even though current tests are cumbersome and not well standardized. Multiple pathways underlie decreased β-cell function and mass, some of which may be shared and may also be a consequence of processes that initially caused dysfunction. Goals for future research include to 1 ) impact the natural history of β-cell failure; 2 ) identify and characterize genetic loci for T2D; 3 ) target β-cell signaling, metabolic, and genetic pathways to improve function/mass; 4 ) develop alternative sources of β-cells for cell-based therapy; 5 ) focus on metabolic environment to provide indirect benefit to β-cells; 6 ) improve understanding of the physiology of responses to bypass surgery; and 7 ) identify circulating factors and neuronal circuits underlying the axis of communication between the brain and β-cells.
413 citations
TL;DR: These findings document that DFU imposes substantial burden on public and private payers, ranging from $9–13 billion in addition to the costs associated with diabetes itself, as well as estimating the annual, per-patient incremental burden of diabetic foot ulcers.
Abstract: OBJECTIVE To estimate the annual, per-patient incremental burden of diabetic foot ulcers (DFUs). RESEARCH DESIGN AND METHODS DFU patients and non-DFU patients with diabetes (controls) were selected using two deidentified databases: ages 65+ years from a 5% random sample of Medicare beneficiaries (Standard Analytical Files, January 2007–December 2010) and ages 18–64 years from a privately insured population (OptumInsight, January 2007–September 2011). Demographics, comorbidities, resource use, and costs from the payer perspective incurred during the 12 months prior to a DFU episode were identified. DFU patients were matched to controls with similar pre-DFU characteristics using a propensity score methodology. Per-patient incremental clinical outcomes (e.g., amputation and medical resource utilization) and health care costs (2012 U.S. dollars) during the 12-month follow-up period were measured among the matched cohorts. RESULTS Data for 27,878 matched pairs of Medicare and 4,536 matched pairs of privately insured patients were analyzed. During the 12-month follow-up period, DFU patients had more days hospitalized (+138.2% Medicare, +173.5% private), days requiring home health care (+85.4% Medicare, +230.0% private), emergency department visits (+40.6% Medicare, +109.0% private), and outpatient/physician office visits (+35.1% Medicare, +42.5% private) than matched controls. Among matched patients, 3.8% of Medicare and 5.0% of privately insured DFU patients received lower limb amputations. Increased utilization resulted in DFU patients having $11,710 in incremental annual health care costs for Medicare, and $16,883 for private insurance, compared with matched controls. Privately insured matched DFU patients incurred excess work-loss costs of $3,259. CONCLUSIONS These findings document that DFU imposes substantial burden on public and private payers, ranging from $9–13 billion in addition to the costs associated with diabetes itself.
405 citations
TL;DR: Coffee consumption was inversely associated with the risk of type 2 diabetes in a dose-response manner and both caffeinated and decaffeinated coffee was associated with reduced diabetes risk.
Abstract: OBJECTIVE Previous meta-analyses identified an inverse association of coffee consumption with the risk of type 2 diabetes. However, an updated meta-analysis is needed because new studies comparing the trends of association for caffeinated and decaffeinated coffee have since been published. RESEARCH DESIGN AND METHODS PubMed and Embase were searched for cohort or nested case-control studies that assessed the relationship of coffee consumption and risk of type 2 diabetes from 1966 to February 2013. A restricted cubic spline random-effects model was used. RESULTS Twenty-eight prospective studies were included in the analysis, with 1,109,272 study participants and 45,335 cases of type 2 diabetes. The follow-up duration ranged from 10 months to 20 years. Compared with no or rare coffee consumption, the relative risk (RR; 95% CI) for diabetes was 0.92 (0.90–0.94), 0.85 (0.82–0.88), 0.79 (0.75–0.83), 0.75 (0.71–0.80), 0.71 (0.65–0.76), and 0.67 (0.61–0.74) for 1–6 cups/day, respectively. The RR of diabetes for a 1 cup/day increase was 0.91 (0.89–0.94) for caffeinated coffee consumption and 0.94 (0.91–0.98) for decaffeinated coffee consumption ( P for difference = 0.17). CONCLUSIONS Coffee consumption was inversely associated with the risk of type 2 diabetes in a dose-response manner. Both caffeinated and decaffeinated coffee was associated with reduced diabetes risk.
388 citations
Wake Forest University1, Colorado School of Public Health2, Centers for Disease Control and Prevention3, Kaiser Permanente4, University of South Carolina5, National Institutes of Health6, University of North Carolina at Chapel Hill7, University of Washington8, Cincinnati Children's Hospital Medical Center9
TL;DR: Prevalence increased with age, was slightly higher in females than males, and was most prevalent in non-Hispanic White and least prevalent in Asian/Pacific Islanders, with Native American and black youth having the highest prevalence of type 2 diabetes.
Abstract: Objective To estimate the prevalence of diabetes in U.S. youth aged Research Design and Methods To address one of its primary aims, the SEARCH for Diabetes in Youth Study identified youth aged Results From a population of 3,458,974 youth aged Conclusion Diabetes mellitus, one of the leading chronic diseases in childhood, affects over 190,000 (1 out of 433) youth less than age 20 years in the US, with racial and ethnic disparities seen in diabetes prevalence, overall and by diabetes type.
TL;DR: DCCT/EDIC provides important information on the influence of glycemic control, and the clinical course of diabetic neuropathy, and on how to prevent neuropathy in type 1 diabetes.
Abstract: OBJECTIVE To describe the development and progression of neuropathy and related findings among patients with type 1 diabetes who participated in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. RESEARCH DESIGN AND METHODS The main diabetic peripheral neuropathy (DPN) outcome was assessed using clinical symptoms, signs, and nerve conduction study results during DCCT and repeated in EDIC year 13/14. Cardiovascular autonomic neuropathy (CAN) was assessed by R-R response to paced breathing, Valsalva ratio, and blood pressure response to standing during DCCT and in EDIC years 13/14 and 16/17. Additionally, symptoms reflecting neuropathic pain and autonomic function (including hypoglycemia awareness) were collected yearly in EDIC using standardized questionnaires; peripheral neuropathy was also assessed annually using the Michigan Neuropathy Screening Instrument. Assessments of genitourinary function were collected at EDIC year 10. RESULTS Intensive therapy during the DCCT significantly reduced the risk of DPN and CAN at DCCT closeout (64% and 45%, respectively, P < 0.01). The prevalence and incidence of DPN and CAN remained significantly lower in the DCCT intensive therapy group compared with the DCCT conventional therapy group through EDIC year 13/14. CONCLUSIONS The persistent effects of prior intensive therapy on neuropathy measures through 14 years of EDIC largely mirror those observed for other diabetes complications. DCCT/EDIC provides important information on the influence of glycemic control, and the clinical course of diabetic neuropathy, and, most important, on how to prevent neuropathy in type 1 diabetes.
TL;DR: The Clinic narrative presented here compares and evaluates AP technology to gain further momentum toward outpatient trials and eventual approval for widespread use, and enumerates the design objectives, variables, and challenges involved in AP development.
Abstract: In this two-part Bench to Clinic narrative, recent advances in both the preclinical and clinical aspects of artificial pancreas (AP) development are described. In the preceding Bench narrative, Kudva and colleagues provide an in-depth understanding of the modified glucoregulatory physiology of type 1 diabetes that will help refine future AP algorithms. In the Clinic narrative presented here, we compare and evaluate AP technology to gain further momentum toward outpatient trials and eventual approval for widespread use. We enumerate the design objectives, variables, and challenges involved in AP development, concluding with a discussion of recent clinical advancements. Thanks to the effective integration of engineering and medicine, the dream of automated glucose regulation is nearing reality. Consistent and methodical presentation of results will accelerate this success, allowing head-to-head comparisons that will facilitate adoption of the AP as a standard therapy for type 1 diabetes.
TL;DR: It is suggested that consumption of sugar-sweetened beverages (SSBs) is related to the risk of diabetes, the metabolic syndrome, and cardiovascular disease, and meta-analyses suggest a gene-SSB potential relationship.
Abstract: Sugar-sweetened drinks have been associated with several health problems. In the point narrative as presented below, we provide our opinion and review of the data to date that we need to reconsider consumption of dietary sugar based on the growing concern of obesity and type 2 diabetes. In the counterpoint narrative following our contribution, Drs. Kahn and Sievenpiper provide a defense and suggest that dietary sugar is not the culprit. Data from the National Health and Nutrition Examination Survey and U.S. Department of Agriculture dietary surveys along with commercial Homescan data on household purchases were used to understand changes in sugar and fructose consumption. Meta-analyses and randomized clinical trials were used to evaluate outcomes of beverage and fructose intake. About 75% of all foods and beverages contain added sugar in a large array of forms. Consumption of soft drinks has increased fivefold since 1950. Meta-analyses suggest that consumption of sugar-sweetened beverages (SSBs) is related to the risk of diabetes, the metabolic syndrome, and cardiovascular disease. Drinking two 16-ounce SSBs per day for 6 months induced features of the metabolic syndrome and fatty liver. Randomized controlled trials in children and adults lasting 6 months to 2 years have shown that lowering the intake of soft drinks reduced weight gain. Recent studies suggest a gene-SSB potential relationship. Consumption of calorie-sweetened beverages has continued to increase and plays a role in the epidemic of obesity, the metabolic syndrome, and fatty liver disease. Reducing intake of soft drinks is associated with less weight gain.
TL;DR: Gla-300 provides more even steady-state PK and PD profiles and a longer duration of action than Gla-100, extending blood glucose control well beyond 24 h, as supported by the later time curves.
Abstract: OBJECTIVE To characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of a new insulin glargine comprising 300 units·mL−1 (Gla-300), compared with insulin glargine 100 units·mL−1 (Gla-100) at steady state in people with type 1 diabetes.
RESEARCH DESIGN AND METHODS A randomized, double-blind, crossover study ( N = 30) was conducted, applying the euglycemic clamp technique over a period of 36 h. In this multiple-dose to steady-state study, participants received once-daily subcutaneous administrations of either 0.4 (cohort 1) or 0.6 units·kg−1 (cohort 2) Gla-300 for 8 days in one treatment period and 0.4 units·kg−1 Gla-100 for 8 days in the other. Here we focus on the results of a direct comparison between 0.4 units·kg−1 of each treatment. PK and PD assessments performed on the last treatment day included serum insulin measurements using a radioimmunoassay and the automated euglycemic glucose clamp technique over 36 h.
RESULTS At steady state, insulin concentration (INS) and glucose infusion rate (GIR) profiles of Gla-300 were more constant and more evenly distributed over 24 h compared with those of Gla-100 and lasted longer, as supported by the later time (∼3 h) to 50% of the area under the serum INS and GIR time curves from time zero to 36 h post dosing. Tight blood glucose control (≤105 mg·dL−1) was maintained for approximately 5 h longer (median of 30 h) with Gla-300 compared with Gla-100.
CONCLUSIONS Gla-300 provides more even steady-state PK and PD profiles and a longer duration of action than Gla-100, extending blood glucose control well beyond 24 h.
TL;DR: This is the first report of gut dysbiosis in Japanese patients with type 2 diabetes as assessed by RT-qPCR, and the high rate of gut bacteria in the circulation suggests translocation of bacteria from the gut to the bloodstream.
Abstract: OBJECTIVE Mounting evidence indicates that the gut microbiota are an important modifier of obesity and diabetes. However, so far there is no information on gut microbiota and “live gut bacteria” in the systemic circulation of Japanese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Using a sensitive reverse transcription–quantitative PCR (RT-qPCR) method, we determined the composition of fecal gut microbiota in 50 Japanese patients with type 2 diabetes and 50 control subjects, and its association with various clinical parameters, including inflammatory markers. We also analyzed the presence of gut bacteria in blood samples. RESULTS The counts of the Clostridium coccoides group, Atopobium cluster, and Prevotella (obligate anaerobes) were significantly lower ( P Lactobacillus (facultative anaerobes) were significantly higher ( P 0.05) in fecal samples of diabetic patients than in those of control subjects. Especially, the counts of Lactobacillus reuteri and Lactobacillus plantarum subgroups were significantly higher ( P P 0.01), and most of these bacteria were Gram-positive. CONCLUSIONS This is the first report of gut dysbiosis in Japanese patients with type 2 diabetes as assessed by RT-qPCR. The high rate of gut bacteria in the circulation suggests translocation of bacteria from the gut to the bloodstream.
TL;DR: In obese, difficult-to-treat patients with T2DM inadequately controlled on high MDI insulin doses, empagliflozin improved glycemic control and reduced weight without increasing the risk of hypoglycemia and with lower insulin requirements.
Abstract: OBJECTIVE We investigated the efficacy and safety of the sodium glucose cotransporter 2 inhibitor, empagliflozin, added to multiple daily injections of insulin (MDI insulin) in obese patients with type 2 diabetes mellitus (T2DM).
RESEARCH DESIGN AND METHODS Patients inadequately controlled on MDI insulin ± metformin (mean HbA1c 8.3% [67 mmol/mol]; BMI 34.8 kg/m2; insulin dose 92 international units/day) were randomized and treated with once-daily empagliflozin 10 mg ( n = 186), empagliflozin 25 mg ( n = 189), or placebo ( n = 188) for 52 weeks. Insulin dose was to remain stable in weeks 1–18, adjusted to meet glucose targets in weeks 19–40, then stable in weeks 41–52. The primary end point was change from baseline in HbA1c at week 18. Secondary end points were changes from baseline in insulin dose, weight, and HbA1c at week 52.
RESULTS Adjusted mean ± SE changes from baseline in HbA1c were −0.50 ± 0.05% (−5.5 ± 0.5 mmol/mol) for placebo versus −0.94 ± 0.05% (−10.3 ± 0.5 mmol/mol) and −1.02 ± 0.05% (−11.1 ± 0.5 mmol/mol) for empagliflozin 10 mg and empagliflozin 25 mg, respectively, at week 18 (both P < 0.001). At week 52, further reductions with insulin titration resulted in changes from baseline in HbA1c of −0.81 ± 0.08% (−8.9 ± 0.9 mmol/mol), −1.18 ± 0.08% (−12.9 ± 0.9 mmol/mol), and −1.27 ± 0.08% (−13.9 ± 0.9 mmol/mol) with placebo, empagliflozin 10 mg, and empagliflozin 25 mg, respectively, and final HbA1c of 7.5% (58 mmol/mol), 7.2% (55 mmol/mol), and 7.1% (54 mmol/mol), respectively. More patients attained HbA1c <7% (<53 mmol/mol) with empagliflozin (31–42%) versus placebo (21%; both P < 0.01). Empagliflozin 10 mg and empagliflozin 25 mg reduced insulin doses (−9 to −11 international units/day) and weight (−2.4 to −2.5 kg) versus placebo (all P < 0.01) at week 52.
CONCLUSIONS In obese, difficult-to-treat patients with T2DM inadequately controlled on high MDI insulin doses, empagliflozin improved glycemic control and reduced weight without increasing the risk of hypoglycemia and with lower insulin requirements.
TL;DR: Empagliflozin 10 and 25 mg for 24 weeks as add-on to metformin therapy significantly improved glycemic control, weight, and BP, and were well-tolerated.
Abstract: OBJECTIVE To investigate the efficacy and tolerability of empagliflozin as an add-on to metformin therapy in patients with type 2 diabetes.
RESEARCH DESIGN AND METHODS Patients with HbA1c levels of ≥7% to ≤ 10% (≥53 to ≤86 mmol/mol) while receiving metformin (≥1,500 mg/day) were randomized and treated with once-daily treatment with empagliflozin 10 mg ( n = 217), empagliflozin 25 mg ( n = 213), or placebo ( n = 207) for 24 weeks. The primary end point was the change in HbA1c level from baseline at week 24. Key secondary end points were changes from baseline in weight and mean daily glucose (MDG) at week 24.
RESULTS At week 24, adjusted mean (SE) changes from baseline in HbA1c were −0.13% (0.05)% (−1.4 [0.5] mmol/mol) with placebo, −0.70% (0.05)% (−7.7 [0.5] mmol/mol) with empagliflozin 10 mg, and −0.77% (0.05)% (−8.4 [0.5] mmol/mol) with empagliflozin 25 mg (both P < 0.001). Empagliflozin significantly reduced MDG level and systolic and diastolic blood pressure (BP) versus placebo. Adjusted mean (SE) changes from baseline in weight were −0.45 kg (0.17 kg) with placebo, −2.08 kg (0.17 kg) with empagliflozin 10 mg, and −2.46 kg (0.17 kg) with empagliflozin 25 mg (both P < 0.001). Adverse events (AEs) were similar across groups (placebo 58.7%; empagliflozin 49.5–57.1%). Confirmed hypoglycemic AEs were reported in 0.5%, 1.8%, and 1.4% of patients receiving placebo, empagliflozin 10 mg, and empagliflozin 25 mg, respectively. Events consistent with urinary tract infections were reported in 4.9%, 5.1%, and 5.6% of patients, and events consistent with genital infections were reported in 0%, 3.7%, and 4.7% of patients, respectively.
CONCLUSIONS Empagliflozin 10 and 25 mg for 24 weeks as add-on to metformin therapy significantly improved glycemic control, weight, and BP, and were well-tolerated.
TL;DR: Gla-300 controls HbA1c as well as Gla-100 for people with type 2 diabetes treated with basal and mealtime insulin but with consistently less risk of nocturnal hypoglycemia.
Abstract: OBJECTIVE To compare the efficacy and safety of new insulin glargine 300 units/mL (Gla-300) with glargine 100 units/mL (Gla-100) in people with type 2 diabetes on basal insulin (≥42 units/day) plus mealtime insulin. RESEARCH DESIGN AND METHODS EDITION 1 (NCT01499082) was a 6-month, multinational, open-label, parallel-group study. Adults with glycated hemoglobin A 1c (HbA 1c ) 7.0–10.0% (53–86 mmol/mol) were randomized to Gla-300 or Gla-100 once daily with dose titration seeking fasting plasma glucose 4.4–5.6 mmol/L. Primary end point was HbA 1c change from baseline; main secondary end point was percentage of participants with one or more confirmed (≤3.9 mmol/L) or severe nocturnal hypoglycemia from week 9 to month 6. RESULTS Participants ( n = 807) had mean age 60 years, diabetes duration 16 years, BMI 36.6 kg/m 2 , and HbA 1c 65.6 mmol/mol (8.15%). HbA 1c reduction was equivalent between regimens; least squares mean difference –0.00% (95% CI –0.11 to 0.11) (–0.00 mmol/mol [–1.2 to 1.2]). Fewer participants reported one or more confirmed (≤3.9 mmol/L) or severe nocturnal hypoglycemic events between week 9 and month 6 with Gla-300 (36 vs. 46% with Gla-100; relative risk 0.79 [95% CI 0.67–0.93]; P CONCLUSIONS Gla-300 controls HbA 1c as well as Gla-100 for people with type 2 diabetes treated with basal and mealtime insulin, but with consistently less risk of nocturnal hypoglycemia.
TL;DR: Findings indicate a high prevalence of diabetes but considerable diversity as a function of Hispanic background and the low rates of diabetes awareness, diabetes control, and health insurance in conjunction with the negative associations between diabetes prevalence and both household income and education among Hispanics/Latinos in the U.S. have important implications for public health policies.
Abstract: OBJECTIVE We examine differences in prevalence of diabetes and rates of awareness and control among adults from diverse Hispanic/Latino backgrounds in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). RESEARCH DESIGN AND METHODS The HCHS/SOL, a prospective, multicenter, population-based study, enrolled from four U.S. metropolitan areas from 2008 to 2011 16,415 18–74-year-old people of Hispanic/Latino descent. Diabetes was defined by either fasting plasma glucose, impaired glucose tolerance 2 h after a glucose load, glycosylated hemoglobin (A1C), or documented use of hypoglycemic agents (scanned medications). RESULTS Diabetes prevalence varied from 10.2% in South Americans and 13.4% in Cubans to 17.7% in Central Americans, 18.0% in Dominicans and Puerto Ricans, and 18.3% in Mexicans ( P P P P = 0.0010) but was negatively related to education ( P = 0.0005) and household income ( P = 0.0043). Rate of diabetes awareness was 58.7%, adequate glycemic control (A1C CONCLUSIONS Present findings indicate a high prevalence of diabetes but considerable diversity as a function of Hispanic background. The low rates of diabetes awareness, diabetes control, and health insurance in conjunction with the negative associations between diabetes prevalence and both household income and education among Hispanics/Latinos in the U.S. have important implications for public health policies.
TL;DR: This study depicts the close association between variations in circulating miRNAs and T2D and their potential relevance in insulin sensitivity.
Abstract: OBJECTIVE This study sought to identify the profile of circulating microRNAs (miRNAs) in type 2 diabetes (T2D) and its response to changes in insulin sensitivity. RESEARCH DESIGN AND METHODS The circulating miRNA profile was assessed in a pilot study of 12 men: 6 with normal glucose tolerance (NGT) and 6 T2D patients. The association of 10 circulating miRNAs with T2D was cross-sectionally validated in an extended sample of 45 NGT vs. 48 T2D subjects (65 nonobese and 28 obese men) and longitudinally in 35 T2D patients who were recruited in a randomized, double-blinded, and placebo-controlled 3-month trial of metformin treatment. Circulating miRNAs were also measured in seven healthy volunteers before and after a 6-h hyperinsulinemic-euglycemic clamp and insulin plus intralipid/heparin infusion. RESULTS Cross-sectional studies disclosed a marked increase of miR-140-5p, miR-142-3p, and miR-222 and decreased miR-423-5p, miR-125b, miR-192, miR-195, miR-130b, miR-532-5p, and miR-126 in T2D patients. Multiple linear regression analyses revealed that miR-140-5p and miR-423-5p contributed independently to explain 49.5% ( P P P = 0.022), miR-140-5p (−15.8%; P = 0.004), and miR-222 (−47.2%; P = 0.03), in parallel to decreased fasting glucose and HbA 1c . Furthermore, while insulin infusion during clamp decreased miR-222 (−62%; P = 0.002), the intralipid/heparin mixture increased circulating miR-222 (163%; P = 0.015) and miR-140-5p (67.5%; P = 0.05). CONCLUSIONS This study depicts the close association between variations in circulating miRNAs and T2D and their potential relevance in insulin sensitivity.
TL;DR: The economic burden associated with diagnosed diabetes (all ages) and undiagnosed diabetes, gestational diabetes, and prediabetes (adults) exceeded $322 billion in 2012, consisting of $244 billion in excess medical costs and $78 billion in reduced productivity, which amounts to an economic burden exceeding $1,000 for each American in 2012.
Abstract: OBJECTIVE To update estimates of the economic burden of undiagnosed diabetes, prediabetes, and gestational diabetes mellitus in 2012 in the U.S. and to present state-level estimates. Combined with published estimates for diagnosed diabetes, these statistics provide a detailed picture of the economic costs associated with elevated glucose levels. RESEARCH DESIGN AND METHODS This study estimated health care use and medical expenditures in excess of expected levels occurring in the absence of diabetes or prediabetes. Data sources that were analyzed include Optum medical claims for ∼4.9 million commercially insured patients who were continuously enrolled from 2010 to 2012, Medicare Standard Analytical Files containing medical claims for ∼2.6 million Medicare patients in 2011, and the 2010 Nationwide Inpatient Sample containing ∼7.8 million hospital discharge records. The indirect economic burden includes reduced labor force participation, missed workdays, and reduced productivity. State-level estimates reflect geographic variation in prevalence, risk factors, and prices. RESULTS The economic burden associated with diagnosed diabetes (all ages) and undiagnosed diabetes, gestational diabetes, and prediabetes (adults) exceeded $322 billion in 2012, consisting of $244 billion in excess medical costs and $78 billion in reduced productivity. Combined, this amounts to an economic burden exceeding $1,000 for each American in 2012. This national estimate is 48% higher than the $218 billion estimate for 2007. The burden per case averaged $10,970 for diagnosed diabetes, $5,800 for gestational diabetes, $4,030 for undiagnosed diabetes, and $510 for prediabetes. CONCLUSIONS These statistics underscore the importance of finding ways to reduce the burden of prediabetes and diabetes through prevention and treatment.
TL;DR: Both once-weekly dulaglutide doses demonstrated superior glycemic control versus placebo and exenatide with an acceptable tolerability and safety profile in type 2 diabetic patients.
Abstract: OBJECTIVE To compare the efficacy and safety of dulaglutide, a once-weekly GLP-1 receptor agonist, with placebo and exenatide in type 2 diabetic patients. The primary objective was to determine superiority of dulaglutide 1.5 mg versus placebo in HbA 1c change at 26 weeks. RESEARCH DESIGN AND METHODS This 52-week, multicenter, parallel-arm study (primary end point: 26 weeks) randomized patients (2:2:2:1) to dulaglutide 1.5 mg, dulaglutide 0.75 mg, exenatide 10 μg, or placebo (placebo-controlled period: 26 weeks). Patients were treated with metformin (1,500–3,000 mg) and pioglitazone (30–45 mg). Mean baseline HbA 1c was 8.1% (65 mmol/mol). RESULTS Least squares mean ± SE HbA 1c change from baseline to the primary end point was −1.51 ± 0.06% (−16.5 ± 0.7 mmol/mol) for dulaglutide 1.5 mg, −1.30 ± 0.06% (−14.2 ± 0.7 mmol/mol) for dulaglutide 0.75 mg, −0.99 ± 0.06% (−10.8 ± 0.7 mmol/mol) for exenatide, and −0.46 ± 0.08% (−5.0 ± 0.9 mmol/mol) for placebo. Both dulaglutide doses were superior to placebo at 26 weeks (both adjusted one-sided P P 1c targets with dulaglutide 1.5 mg and 0.75 mg than with placebo and exenatide (all P CONCLUSIONS Both once-weekly dulaglutide doses demonstrated superior glycemic control versus placebo and exenatide with an acceptable tolerability and safety profile.
TL;DR: The application of the new IADPSGC was associated with a 3.5-fold increase in GDM prevalence in the study population, as well as significant improvements in pregnancy outcomes, and was cost-effective.
Abstract: OBJECTIVE The use of the new International Association of the Diabetes and Pregnancy Study Groups criteria (IADPSGC) for the diagnosis of gestational diabetes mellitus (GDM) results in an increased prevalence of GDM. Whether their introduction improves pregnancy outcomes has yet to be established. We sought to evaluate the cost-effectiveness of one-step IADPSGC for screening and diagnosis of GDM compared with traditional two-step Carpenter-Coustan (CC) criteria.
RESEARCH DESIGN AND METHODS GDM risk factors and pregnancy and newborn outcomes were prospectively assessed in 1,750 pregnant women from April 2011 to March 2012 using CC and in 1,526 pregnant women from April 2012 to March 2013 using IADPSGC between 24 and 28 weeks of gestation. Both groups received the same treatment and follow-up regimes.
RESULTS The use of IADPSGC resulted in an important increase in GDM rate (35.5% vs. 10.6%) and an improvement in pregnancy outcomes, with a decrease in the rate of gestational hypertension (4.1 to 3.5%: −14.6%, P < 0.021), prematurity (6.4 to 5.7%: −10.9%, P < 0.039), cesarean section (25.4 to 19.7%: −23.9%, P < 0.002), small for gestational age (7.7 to 7.1%: −6.5%, P < 0.042), large for gestational age (4.6 to 3.7%: −20%, P < 0.004), Apgar 1-min score <7 (3.8 to 3.5%: −9%, P < 0.015), and admission to neonatal intensive care unit (8.2 to 6.2%: −24.4%, P < 0.001). Estimated cost savings was of €14,358.06 per 100 women evaluated using IADPSGC versus the group diagnosed using CC.
CONCLUSIONS The application of the new IADPSGC was associated with a 3.5-fold increase in GDM prevalence in our study population, as well as significant improvements in pregnancy outcomes, and was cost-effective. Our results support their adoption.
TL;DR: Consistency of glycemic control is important to reduce the risks of vascular events and death in type 2 diabetes.
Abstract: OBJECTIVE There is no consensus on the importance of visit-to-visit glycemic variability in diabetes. Therefore, we assessed the effects of visit-to-visit variability (VVV) in HbA 1c and fasting glucose on major outcomes in the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation) trial. RESEARCH DESIGN AND METHODS ADVANCE was a factorial randomized controlled trial of intensive glucose control and blood pressure lowering in patients with type 2 diabetes. VVV in the intensive glucose treatment group was defined using the SD of five measurements of HbA 1c and glucose taken 3–24 months after randomization. Outcomes were combined macro- and microvascular events and all-cause mortality occurring post 24 months. Sensitivity analyses were performed using other indices of variability and in the standard glucose treatment group. RESULTS Among 4,399 patients in the intensive group, an increase in VVV of HbA 1c was associated with an increased risk of vascular events ( P = 0.01) and with mortality ( P P 1c variability was positively associated with the risk of macrovascular events ( P = 0.02 for trend), whereas glucose variability was associated with both macro- and microvascular events ( P = 0.005 and P CONCLUSIONS Consistency of glycemic control is important to reduce the risks of vascular events and death in type 2 diabetes.
TL;DR: Dulaglutide improves glycemic control and is well tolerated as monotherapy in patients with early stage type 2 diabetes, and meets HbA1c targets.
Abstract: OBJECTIVE Compare the efficacy and safety of monotherapy with dulaglutide, a once-weekly GLP-1 receptor agonist, to metformin-treated patients with type 2 diabetes. The primary objective compared dulaglutide 1.5 mg and metformin on change from baseline glycosylated hemoglobin A 1c (HbA 1c ) at 26 weeks. RESEARCH DESIGN AND METHODS This 52-week double-blind study randomized patients to subcutaneous dulaglutide 1.5 mg, dulaglutide 0.75 mg, or metformin. Patients ( N = 807) had HbA 1c ≥6.5% (≥48 mmol/mol) and ≤9.5% (≤80 mmol/mol) with diet and exercise alone or low-dose oral antihyperglycemic medication (OAM) monotherapy; OAMs were discontinued at beginning of lead-in period. RESULTS At 26 weeks, changes from baseline HbA 1c (least squares [LS] mean ± SE) were: dulaglutide 1.5 mg, −0.78 ± 0.06% (−8.5 ± 0.70 mmol/mol); dulaglutide 0.75 mg, −0.71 ± 0.06% (−7.8 ± 0.70 mmol/mol); and metformin, −0.56 ± 0.06% (−6.1 ± 0.70 mmol/mol). Dulaglutide 1.5 and 0.75 mg were superior to metformin (LS mean difference): −0.22% (−2.4 mmol/mol) and −0.15% (−1.6 mmol/mol) (one-sided P 1c targets P CONCLUSIONS Dulaglutide improves glycemic control and is well tolerated as monotherapy in patients with early stage type 2 diabetes.
TL;DR: CGM use is uncommon but associated with lower HbA1c in some age-groups, especially when used more frequently, and factors associated with discontinuation and infrequent use of retrospective analysis of CGM data should be considered in developing next-generation devices and education on CGM use.
Abstract: OBJECTIVE To assess the frequency of continuous glucose monitoring (CGM) device use, factors associated with its use, and the relationship of CGM with diabetes outcomes (HbA1c, severe hypoglycemia [SH], and diabetic ketoacidosis [DKA])
RESEARCH DESIGN AND METHODS Survey questions related to CGM device use 1 year after enrollment in the T1D Exchange clinic registry were completed by 17,317 participants Participants were defined as CGM users if they indicated using real-time CGM during the prior 30 days
RESULTS Nine percent of participants used CGM (6% of children <13 years old, 4% of adolescents 13 to <18 years, 6% of young adults 18 to <26 years, and 21% of adults ≥26 years) CGM use was more likely with higher education, higher household income, private health insurance, longer duration of diabetes, and use of insulin pump ( P < 001 all factors) CGM use was associated with lower HbA1c in children (83% vs 86%, P < 0001) and adults (77% vs 79%, P < 0001) In adults, more frequent use of CGM (≥6 days/week) was associated with lower mean HbA1c Only 27% of users downloaded data from their device at least once per month, and ≤15% of users reported downloading their device at least weekly Among participants who used CGM at baseline, 41% had discontinued within 1 year
CONCLUSIONS CGM use is uncommon but associated with lower HbA1c in some age-groups, especially when used more frequently Factors associated with discontinuation and infrequent use of retrospective analysis of CGM data should be considered in developing next-generation devices and education on CGM use
TL;DR: The incidence of both GDM and pre-GDM in pregnancy has doubled over the last 14 years, and the overall burden of diabetes in pregnancy on society is growing.
Abstract: OBJECTIVE Women with diabetes in pregnancy have high rates of pregnancy complications. Our aims were to explore trends in the incidence of diabetes in pregnancy and examine whether the risk of serious perinatal outcomes has changed. RESEARCH DESIGN AND METHODS We performed a population-based cohort study of 1,109,605 women who delivered in Ontario, Canada, between 1 April 1996 and 31 March 2010. We categorized women as gestational diabetes (GDM) ( n = 45,384), pregestational diabetes (pre-GDM) ( n = 13,278), or no diabetes ( n = 1,050,943). The annual age-adjusted rates of diabetes in pregnancy were calculated, and rates of serious perinatal outcomes were compared between groups and by year using Poisson regression. RESULTS The age-adjusted rate of both GDM (2.7–5.6%, P P CONCLUSIONS The incidence of both GDM and pre-GDM in pregnancy has doubled over the last 14 years, and the overall burden of diabetes in pregnancy on society is growing. Although congenital anomaly rates have declined in women with diabetes, perinatal mortality rates remain unchanged, and the risk of both remains significantly elevated compared with nondiabetic women. Increased efforts are needed to reduce these adverse outcomes.
TL;DR: The results suggest that in patients with type 2 diabetes, inadequately controlled on sitagliptin with or without metformin, add-on treatment with dapagliflozin provides additional clinical benefit and is well tolerated.
Abstract: OBJECTIVE To assess the efficacy and safety of dapagliflozin as add-on therapy in patients with type 2 diabetes who were inadequately controlled with a dipeptidyl peptidase-4 inhibitor with or without metformin. RESEARCH DESIGN AND METHODS In this 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 study with a 24-week blinded extension period, 432 patients were randomized to receive dapagliflozin 10 mg/day or placebo added to sitagliptin (100 mg/day) ± metformin (≥1,500 mg/day). RESULTS Baseline HbA 1c and FPG levels were 7.9% (63.0 mmol/mol) and 162.2 mg/dL (9.0 mmol/L) for the dapagliflozin group and 8.0% (64.0 mmol/mol) and 163 mg/dL (9.0 mmol/L) for placebo. At week 24, dapagliflozin significantly reduced mean HbA 1c levels (–0.5% [–4.9 mmol/mol]) versus placebo (0.0% [+0.4 mmol/mol]). Dapagliflozin reduced body weight versus placebo (–2.1 and –0.3 kg) and reduced HbA 1c levels in patients with baseline values ≥8.0% (–0.8% [8.7 mmol/mol] and 0.0% [0.3 mmol/mol]) and fasting plasma glucose levels (–24.1 mg/dL [–1.3 mmol/L] and 3.8 mg/dL [0.2 mmol/L]). Similar results were observed when data were stratified by background therapy. Glycemic and weight benefits observed at week 24 were maintained through week 48. Changes from baseline in systolic blood pressure at week 8 were not significantly different between treatment groups. Over 48 weeks, fewer patients receiving dapagliflozin were discontinued or rescued for failing to achieve glycemic targets compared with placebo. Adverse events were balanced between groups, and discontinuation rates were low. At week 48, signs and symptoms suggestive of genital infection were more frequent with dapagliflozin (9.8%) than with placebo (0.4%). Signs and symptoms suggestive of urinary tract infection were balanced between dapagliflozin (6.7%) and placebo (6.2%). CONCLUSIONS These results suggest that in patients with type 2 diabetes, inadequately controlled on sitagliptin with or without metformin, add-on treatment with dapagliflozin provides additional clinical benefit and is well tolerated.
TL;DR: Both dulaglutide doses demonstrated superior glycemic control versus sitagliptin at 52 weeks with an acceptable tolerability and safety profile.
Abstract: OBJECTIVE To compare the efficacy and safety of two doses of once-weekly dulaglutide, a glucagon-like peptide 1 receptor agonist, to sitagliptin in uncontrolled, metformin-treated patients with type 2 diabetes. The primary objective was to compare (for noninferiority and then superiority) dulaglutide 1.5 mg versus sitagliptin in change from baseline in glycosylated hemoglobin A1c (HbA1c) at 52 weeks.
RESEARCH DESIGN AND METHODS This multicenter, adaptive, double-blind, parallel-arm study randomized patients ( N = 1,098; mean baseline age 54 years; HbA1c 8.1% [65 mmol/mol]; weight 86.4 kg; diabetes duration 7 years) to dulaglutide 1.5 mg, dulaglutide 0.75 mg, sitagliptin 100 mg, or placebo (placebo-controlled period up to 26 weeks). The treatment period lasted 104 weeks, with 52-week primary end point data presented.
RESULTS The mean HbA1c changes to 52 weeks were (least squares mean ± SE): −1.10 ± 0.06% (−12.0 ± 0.7 mmol/mol), −0.87 ± 0.06% (9.5 ± 0.7 mmol/mol), and −0.39 ± 0.06% (4.3 ± 0.7 mmol/mol) for dulaglutide 1.5 mg, dulaglutide 0.75 mg, and sitagliptin, respectively. Both dulaglutide doses were superior to sitagliptin ( P < 0.001, both comparisons). No events of severe hypoglycemia were reported. Mean weight changes to 52 weeks were greater with dulaglutide 1.5 mg (−3.03 ± 0.22 kg) and dulaglutide 0.75 mg (−2.60 ± 0.23 kg) compared with sitagliptin (−1.53 ± 0.22 kg) ( P < 0.001, both comparisons). The most common gastrointestinal treatment-emergent adverse events in dulaglutide 1.5- and 0.75-mg arms were nausea, diarrhea, and vomiting.
CONCLUSIONS Both dulaglutide doses demonstrated superior glycemic control versus sitagliptin at 52 weeks with an acceptable tolerability and safety profile.