Dose-Response Effects of Insulin Glargine in Type 2 Diabetes

Abstract

OBJECTIVETo determine the pharmacokinetic and pharmacodynamic dose-response effects of insulin glargine administered subcutaneously in individuals with type 2 diabetes.RESEARCH DESIGN AND METHODSTwenty obese type 2 diabetic individuals (10 male and 10 female, aged 50 ± 3 years, with BMI 36 ± 2 kg/m2 and A1C 8.3 ± 0.6%) were studied in this single-center, placebo-controlled, randomized, double-blind study. Five subcutaneous doses of insulin glargine (0, 0.5, 1.0, 1.5, and 2.0 units/kg) were investigated on separate occasions using the 24-h euglycemic clamp technique.RESULTSGlargine duration of action to reduce glucose, nonessential fatty acid (NEFA), and β-hydroxybutyrate levels was close to or >24 h for all four doses. Increases in glucose flux revealed no discernible peak and were modest with maximal glucose infusion rates of 9.4, 6.6, 5.5, and 2.8 μmol/kg/min for the 2.0, 1.5, 1.0, and 0.5 units/kg doses, respectively. Glargine exhibited a relatively hepatospecific action with greater suppression (P < 0.05) of endogenous glucose production (EGP) compared with little or no increases in glucose disposal.CONCLUSIONA single subcutaneous injection of glargine at a dose of ≥0.5 units/kg can acutely reduce glucose, NEFA, and ketone body levels for 24 h in obese insulin-resistant type 2 diabetic individuals. Glargine lowers blood glucose by mainly inhibiting EGP with limited effects on stimulating glucose disposal. Large doses of glargine have minimal effects on glucose flux and retain a relatively hepatospecific action in type 2 diabetes.

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

“…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.…”

“…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. Alternatively, a bedtime snack is not advised and frequently not consumed by subjects on AM administration of insulin glargine because of a distinctly less concern of nocturnal hypoglycemia on part of both patients and providers since nocturnal hypoglycemia is significantly less frequently documented in studies using insulin glargine in AM [3,[4][5][6][7][8]. Thus, the difference in total daily caloric consumption may contribute to these different outcomes regarding body weights in subjects receiving insulin glargine.…”

“…Prior to transition, insulin glargine was administered in AM prior to breakfast since the AM administration in combination with oral agents has resulted in better glycemic control without weight gain in some previous studies [3][4][5][6]. Moreover, once daily administration of insulin glargine may be appropriate at any dose since the 24 hour profile remains stable without peaks and troughs even at a dose as high as 2 units/KG body weight in subjects with type 2 Diabetes [7,8]. Outcomes for assessment were predetermined and included glycemic control (HbA1c), body weight and daily insulin dose.…”

Pharmacokinetics and Pharmacodynamics of Insulin Glargine Given in the Evening as Compared With in the Morning in Type 2 Diabetes

“…Yet, an indirect comparison of PK and PD between studies, where glargine was given in the evening (14) compared with the morning (15)(16)(17), suggests important differences in action profiles, although in such a comparison the contribution of circadian changes in insulin sensitivity should be taken into account (18,19).…”

Evaluation of Safety and Efficacy of Glaritus&lt;sup&gt;&amp;reg;&lt;/sup&gt; versus Lantus&lt;sup&gt;&amp;reg;&lt;/sup&gt; in Combination with Insulin Lispro among Adults with Type 1 Diabetes Mellitus-Phase IV Study

“…A systematic review by Wang et al showed that insulin glargine is effective in the management of T1DM and provides consistent insulin delivery which ensures effective glycemic control for 24 hours making it suitable for once daily dosing [15].…”