Insulin detemir versus insulin glargine for type 2 diabetes mellitus

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. To assess the effects of insulin detemir and insulin glargine compared with each other in the treatment of type 2 diabetes mellitus. We searched MEDLINE, EMBASE, The Cochrane Library, online registries of ongoing trials and abstract books. Date of last search was January 2011. All randomised controlled trials comparing insulin detemir with insulin glargine with a duration of 12 weeks or longer were included. Two authors independently selected the studies and extracted the data. Pooling of studies by means of random-effects meta-analysis was performed. 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. 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 reaction

Rationale, Design, and Baseline Data of the Insulin Glargine (Lantus) Versus Insulin Detemir (Levemir) Treat-To-Target (L2T3) Study: A Multinational, Randomized Noninferiority Trial of Basal Insulin Initiation in Type 2 Diabetes

Objective: To discuss the design and baseline data of the Lantus (R) (sanofi-aventis, Paris, France) versus Levemir (R) (Novo Nordisk A/S, Bagsvaerd, Denmark) Treat-To-Target (L2T3) study, a multinational, randomized comparison between the basal insulin analogs insulin glargine and insulin detemir. Methods: Insulin-naive subjects with type 2 diabetes suboptimally controlled on oral glucose-lowering drugs (OGLDs) (including at least metformin) were randomized to 24-week treatment with either insulin glargine once-daily or insulin detemir twice-daily, titrated to obtain fasting plasma glucose <100 mg/dL. The primary outcome was the percentage of subjects reaching hemoglobin A1c (HbA1c) <7% without symptomatic confirmed hypoglycemia. Important secondary outcomes were quality of life and treatment satisfaction, which were repeatedly assessed using validated questionnaires. Also, biomedical and psychological determinants of failure to reach HbA1c <7% were explored. Results: Recruitment was completed in November 2007. The majority of the randomized population (n = 973) was white (77.8%) and used one other OGLD beside metformin (70.7%). Concerning patient-reported outcomes, similar to 20% of subjects reported no physical symptoms of fatigue or hyperglycemia before insulin initiation, and similar to 10% were maximally satisfied with their previous treatment. One-third of patients (29.9%) reported suboptimal well-being, and 9.3% had a score indicating depression. Better emotional well-being was significantly associated with lower diabetes symptom distress and higher treatment satisfaction (respectively, r = -0.56 and 0.41; P <0.001). Conclusions: The L2T3 study will extend the evidence on both the efficacy and the effects on quality of life and treatment satisfaction of the long-acting insulin analogs glargine and detemir. Additionally, it will increase our understanding of the factors important to the (self-) management of type 2 diabetes patients starting insuli

Fatty acid desaturation by stearoyl-CoA desaturase-1 controls regulatory T cell differentiation and autoimmunity

The imbalance between pathogenic and protective T cell subsets is a cardinal feature of autoimmune disorders such as multiple sclerosis (MS). Emerging evidence indicates that endogenous and dietary-induced changes in fatty acid metabolism have a major impact on both T cell fate and autoimmunity. To date, however, the molecular mechanisms that underlie the impact of fatty acid metabolism on T cell physiology and autoimmunity remain poorly understood. Here, we report that stearoyl-CoA desaturase-1 (SCD1), an enzyme essential for the desaturation of fatty acids and highly regulated by dietary factors, acts as an endogenous brake on regulatory T-cell (Treg) differentiation and augments autoimmunity in an animal model of MS in a T cell-dependent manner. Guided by RNA sequencing and lipidomics analysis, we found that the absence of Scd1 in T cells promotes the hydrolysis of triglycerides and phosphatidylcholine through adipose triglyceride lipase (ATGL). ATGL-dependent release of docosahexaenoic acid enhanced Treg differentiation by activating the nuclear receptor peroxisome proliferator-activated receptor gamma. Our findings identify fatty acid desaturation by SCD1 as an essential determinant of Treg differentiation and autoimmunity, with potentially broad implications for the development of novel therapeutic strategies and dietary interventions for autoimmune disorders such as MS