Relationship of Insulin Dose, A1c Lowering, and Weight in Type 2 Diabetes: Comparing Insulin Glargine and Insulin Detemir

Abstract

Background: A pooled analysis of randomized controlled trials of individuals with type 2 diabetes mellitus (T2DM) was conducted to compare dosing and impact of two basal insulin analogs, insulin glargine (glargine) and insulin detemir (detemir), on weight and hemoglobin A1c (A1c). Methods: Twenty-two studies of at least 20 weeks in duration in individuals with T2DM initiating glargine/ detemir were included. Results were combined using a weighted-average method and a bivariate random effect model. Outcomes included changes in weight, A1c, and insulin dose from study start to end. Results: One study was head-to-head comparison of glargine and detemir. Detemir (four studies) was administered once or twice daily, with 50% starting on detemir once daily but needing therapy intensification. Glargine was used once daily in all 22 studies. The Egger test was borderline significant for change in weight over the course of the treatment for glargine (0.29; 90% confidence interval [CI] À0.01, 0.58), and heterogeneity was not observed for detemir (À0.18; 90% CI À0.59, 0.23). Heterogeneity was observed for change in A1c over the course of the treatment (glargine, À1.19, 90% CI À1.74, À0.63; detemir, À2.65, 90% CI À4.86, À0.45). Nonheterogeneity for change in A1c over the course of the treatment was achieved by excluding five studies for glargine and one study for detemir; however, all studies were included in subsequent analyses. In the unadjusted model, glargine and detemir showed similar results for mean A1c change (À1.4% vs. À1.4%), weight gain (2.5 vs. 1.7 kg), and weight/A1c (1.8 vs. 1.2 kg/%). A significantly higher detemir dose was needed to achieve the same A1c change (51.5 vs. 38.8 U/day). Conclusions: Although absolute weight gain was higher with glargine versus detemir, weight gain per A1c change was similar. A higher detemir dose was required to achieve a similar A1c reduction.

Iowa medicaid 2: lapse of glycemic control on abrupt transition from insulin glargine to insulin detemir in type 2 diabetes mellitus

“…This finding is consistent with observations in another study in which a substantial reduction in daily dose of insulin glargine was noted with a transition from insulin detemir in subjects with type 2 Diabetes [9]. Several other studies have also documented a requirement of a higher daily dose of insulin detemir in comparison to insulin glargine to attain comparable glycemic control [10][11][12][13][14][15][16][17][18][19]. Thus, a higher daily dose and twice daily administration of insulin detemir may have been required to achieve desirable glycemic goal in this study as documented in previous studies in most subjects with both Type 1 and Type 2 diabetes [1,[10][11][12][13][14][15][16][17][18][19].…”

“…The differences in changes in body weights observed in earlier studies [12][13][14][15]17] in comparison to our present data may be attributed to the different times during the day at which insulin glargine was administered. Lack of significant weight gain in our subjects in Group 2 is likely to be secondary to the administration of insulin glargine in AM as reported in other previous studies [3,[5][6][7][8] whereas the significant weight gain noted in other studies [12][13][14][15]17] may be attributed to bedtime administration of insulin glargine. Weight gain in subjects receiving insulin glargine at bedtime may be due to a consumption of a snack following insulin administration because of the concern of nocturnal hypoglycemia on part of both patients and providers alike especially because of a fairly large dose required by most obese subjects with type 2 Diabetes.…”

“…A significantly greater weight gain was documented in subjects with type 2 Diabetes on attaining similar glycemic control with insulin glargine administered once daily in comparison with insulin detemir administered once or twice daily despite a significantly smaller daily dose [12][13][14][15]17]. In contrast, no significant weight gain was noted in subjects continuing insulin glargine in this study.…”

“…Several other studies have also documented a requirement of a higher daily dose of insulin detemir in comparison to insulin glargine to attain comparable glycemic control [10][11][12][13][14][15][16][17][18][19]. Thus, a higher daily dose and twice daily administration of insulin detemir may have been required to achieve desirable glycemic goal in this study as documented in previous studies in most subjects with both Type 1 and Type 2 diabetes [1,[10][11][12][13][14][15][16][17][18][19]. The requirement for a higher daily dose for insulin detemir in comparison to insulin glargine in order to achieve identical glycemic control in type 2 Diabetes is further confirmed in a recent study examining pharmacokinetics and pharmacodynamics of these insulins [20].…”

HARMONY 4: randomised clinical trial comparing once-weekly albiglutide and insulin glargine in patients with type 2 diabetes inadequately controlled with metformin with or without sulfonylurea

“…Long-acting, or basal insulin, which is dosed once a day and provides relatively constant blood levels over 24 h, is typically the first type of insulin added to the treatment regimen [2]. As is true with other forms of insulin, the use of basal insulin is associated with weight gain and hypoglycaemia [3,4]. Hypoglycaemia and weight gain are factors that influence tolerability and compliance of insulin therapy in type 2 diabetes [5,6].…”