Aim
Hypoglycaemia and the fear of hypoglycaemia are barriers to achieving normoglycaemia with insulin. Insulin degludec (IDeg) has an ultra-long and stable glucose-lowering effect, with low day-to-day variability. This pre-planned meta-analysis aimed to demonstrate the superiority of IDeg over insulin glargine (IGlar) in terms of fewer hypoglycaemic episodes at equivalent HbA1c in type 2 and type 1 diabetes mellitus (T2DM/T1DM).

Methods
Pooled patient-level data for self-reported hypoglycaemia from all seven (five in T2DM and two in T1DM) randomized, controlled, phase 3a, treat-to-target trials in the IDeg clinical development programme comparing IDeg once-daily (OD) vs. IGlar OD were analysed.

Results
Four thousand three hundred and thirty subjects (2899 IDeg OD vs. 1431 IGlar OD) were analysed. Among insulin-naive T2DM subjects, significantly lower rates of overall confirmed, nocturnal confirmed and severe hypoglycaemic episodes were reported with IDeg vs. IGlar: estimated rate ratio (RR):0.83[0.70;0.98]95%CI, RR:0.64[0.48;0.86]95%CI and RR:0.14[0.03;0.70]95%CI. In the overall T2DM population, significantly lower rates of overall confirmed and nocturnal confirmed episodes were reported with IDeg vs. IGlar [RR:0.83[0.74;0.94]95%CI and RR:0.68[0.57;0.82]95%CI). In the T1DM population, the rate of nocturnal confirmed episodes was significantly lower with IDeg vs. IGlar during maintenance treatment (RR:0.75[0.60;0.94]95%CI). Reduction in hypoglycaemia with IDeg vs. IGlar was more pronounced during maintenance treatment in all populations.

Conclusions
The limitations of this study include the open-label design and exclusion of subjects with recurrent severe hypoglycaemia. This meta-analysis confirms that similar improvements in HbA1c can be achieved with fewer hypoglycaemic episodes, particularly nocturnal episodes, with IDeg vs. IGlar across a broad spectrum of patients with diabetes.

https://dom-pubs.onlinelibrary.wiley.com/doi/pdf/10.1111/dom.12032

Hypoglycaemia risk with insulin degludec compared with insulin glargine in type 2 and type 1 diabetes: a pre-planned meta-analysis of phase 3 trials

http://www.edizioniscriptamanent.it/sites/default/files/app/medicine-planet/06-02clarkw.comment.pdf

Association of a difference in systolic blood pressure between arms with vascular disease and mortality: a systematic review and meta-analysis

Type 2 diabetes and cardiovascular disease in South Asians

Objective: Prediabetes is a high-risk state for developing diabetes and associated complications. The purpose of this paper was to report trends in prevalence of prediabetes for individuals aged 16 and older in England without previously diagnosed diabetes.

https://bmjopen.bmj.com/content/bmjopen/4/6/e005002.full.pdf

Prevalence of prediabetes in England from 2003 to 2011: population-based, cross-sectional study

Background
Chronically elevated blood glucose levels are associated with significant morbidity and mortality. Many diabetes patients will eventually require insulin treatment to maintain good glycaemic control. There are still uncertainties about the optimal insulin treatment regimens for type 2 diabetes, but the long-acting insulin analogues seem beneficial. Several reviews have compared either insulin detemir or insulin glargine to NPH insulin, but research directly comparing both insulin analogues is limited.

Objectives
To assess the effects of insulin detemir and insulin glargine compared with each other in the treatment of type 2 diabetes mellitus.

Search methods
We searched MEDLINE, EMBASE, The Cochrane Library, online registries of ongoing trials and abstract books. Date of last search was January 2011.

Selection criteria
All randomised controlled trials comparing insulin detemir with insulin glargine with a duration of 12 weeks or longer were included.

Data collection and analysis
Two authors independently selected the studies and extracted the data. Pooling of studies by means of random-effects meta-analysis was performed.

Main results
This review examined four trials lasting 24 to 52 weeks involving 2250 people randomised to either insulin detemir or glargine. Overall, risk of bias of the evaluated studies was high. Insulin glargine was dosed once-daily in the evening. Insulin detemir was initiated once-daily in the evening with the option of an additional dose in the morning in three studies and initiated twice-daily in one study. Of randomised patients 13.6% to 57.2% were injecting insulin detemir twice-daily at the end of trial.

Glycaemic control, measured by glycosylated haemoglobin A1c (HbA1c) and HbA1c equal to or less than 7% with or without hypoglycaemia, did not differ statistically significantly between treatment groups.

The results showed no significant differences in overall, nocturnal and severe hypoglycaemia between treatment groups.

Insulin detemir was associated with less weight gain. Treatment with insulin glargine resulted in a lower daily basal insulin dose and a lower number of injection site reactions.

There was no significant difference in the variability of FPG or glucose values in 24-hour profiles between treatment groups. It was not possible to draw conclusions on quality of life, costs or mortality. Only one trial reported results on health-related quality of life and showed no significant differences between treatment groups.

Authors' conclusions
Our analyses suggest that there is no clinically relevant difference in efficacy or safety between insulin detemir and insulin glargine for targeting hyperglycaemia. However, to achieve the same glycaemic control insulin detemir was often injected twice-daily in a higher dose but with less weight gain, while insulin glargine was injected once-daily, with somewhat fewer injection site reactions.

Insulin detemir versus insulin glargine for type 2 diabetes mellitus.

OBJECTIVE To determine whether glargine is noninferior to detemir regarding the percentage of patients reaching A1C RESEARCH DESIGN AND METHODS In this 24-week trial, 973 insulin-naive type 2 diabetic patients on stable oral glucose-lowering drugs with A1C 7.0–10.5% were randomized to glargine once daily or detemir twice daily. Insulin doses were systematically titrated. RESULTS 27.5 and 25.6% of patients reached the primary outcome with glargine and detemir, respectively, demonstrating the noninferiority of glargine. Improvements in A1C were −1.46 ± 1.09% for glargine and −1.54 ± 1.11% for detemir ( P = 0.149), with similar proportions of patients achieving A1C P = 0.254) but more detemir-treated patients reaching A1C P = 0.017). Hypoglycemia risk was similar. Weight gain was higher for glargine (difference: 0.77 kg, P P CONCLUSIONS In insulin-naive type 2 diabetic patients, glargine reached similar control as detemir, with more weight gain, but required significantly lower doses.

https://care.diabetesjournals.org/content/diacare/33/6/1176.full.pdf

A 24-Week, Randomized, Treat-to-Target Trial Comparing Initiation of Insulin Glargine Once-Daily With Insulin Detemir Twice-Daily in Patients With Type 2 Diabetes Inadequately Controlled on Oral Glucose-Lowering Drugs

The handbook, commissioned by the UK National Screening Committee [UK NSC],
 Describes the context, and outlines evidence for a co-ordinated vascular disease control programme to
identify and reduce risks of cardiovascular disease in the population.
 Suggests aims, objectives and a delivery strategy framework appropriate for a Cardiovascular Disease
(CVD) risk management programme.
 Reports key messages from the Diabetes, Heart Disease & Stroke (DHDS) pilot project.
 Provides examples of tools, resources and standard operating procedures that can be used by health
professionals, many of whom are already undertaking some CVD risk assessment in a variety of ways.

The Handbook for Vascular Risk Assessment, Risk Reduction and Risk Management

Type 2 diabetes mellitus (T2DM) is a well-recognized risk factor for the development of cardiovascular disease. With an increasing prevalence of obesity, this risk has increased further. Management of T2DM in obese patients is particularly challenging as treatment with the majority of glucose-lowering agents results in weight gain. Thus, the development of a therapeutic option which could improve glycemic control without weight gain or hypoglycemia, such as the glucagon-like peptide-1 (GLP-1) analog exenatide, is a welcome addition to the currently available therapies in the management of T2DM. With recognition and better understanding of the role of incretin hormones in T2DM, exenatide was developed and introduced into clinical practice in 2005. Both randomized controlled trials and retrospective observational studies have shown that treatment with exenatide not only improves glycemic control, with a low risk of hypoglycemia, but also results in concurrent weight loss and the additional benefit of improvement in cardiovascular risk factors. This article will provide an overview of both short- and long-acting exenatide in the management of T2DM and associated cardiovascular risk factors.

/pdf/a-review-of-exenatide-optimizing-glycemic-control-and-2u0y25vydy.pdf

Melanie Davies

Papers

A 24-Week, Randomized, Treat-to-Target Trial Comparing Initiation of Insulin Glargine Once-Daily With Insulin Detemir Twice-Daily in Patients With Type 2 Diabetes Inadequately Controlled on Oral Glucose-Lowering Drugs

The Handbook for Vascular Risk Assessment, Risk Reduction and Risk Management

A review of exenatide: optimizing glycemic control and associated cardiovascular risk factors in type 2 diabetes.