1102-P: High vs. Standard Starting Dose of Insulin Glargine 100 U/ml in Patients with Overweight/Obesity and Type 2 Diabetes Uncontrolled with Oral Antidiabetic Drugs in China: A Multicenter, Open-Label Randomized Controlled Trial

With type 2 diabetes (T2D) progression, patients require insulin, but insufficient titration often leads to poor glycemic control. A higher insulin starting dose may reduce the optimal dose deficit, but whether this procedure increases hypoglycemia risk is unknown. This open-label, multicenter trial (NCT02836704) evaluated safety and efficacy of a high (0.3 U/kg) vs. standard (0.2 U/kg) starting dose of glargine 100 U/ml (Gla-100) followed by titration over 16 weeks to achieve self-monitored FBG 4.4-5.6 mmol/L using the same algorithm in each group. Overall, 892 patients with overweight/obesity (BMI 25-40 kg/m2) and uncontrolled T2D (HbA1c 7.5-11.0%; lab FPG >9.0 mmol/L) on stable doses of 2-3 OADs were randomized to receive a high (n=444) or standard (n=448) starting dose of Gla-100. At week 16, 92% of patients completed the study and 866 were analyzed. The primary endpoint (percentage of patients with ≥1 confirmed hypoglycemia, BG <3.9 mmol/L) met the pre-specified threshold (upper bound 95% CI <10%) for non-inferiority of Gla-100 0.3 U/kg vs. 0.2 U/kg with 11.0% and 8.6% in the respective groups (log-binomial regression estimated difference 2.1%; 95% CI: −1.68%, 5.89%). At week 16, symptomatic (9.8% vs. 7.0%, p=0.13) and nocturnal hypoglycemia (2.7% vs. 1.2%, p=0.10), percentage of patients achieving HbA1c <7.0% without hypoglycemia (37.1% vs. 37.1%), and percentage of patients achieving lab FPG targets <5.6 mmol/L (15.9% vs. 16.3%), <6.1 mmol/L (27.6% vs. 26.1%), or <7.0 mmol/L (48.8% vs. 48.3%) were all similar in both groups. However, time to achieve first self-monitored FBG <5.6, <6.1, or <7 mmol/L was 6, 9, and 7 days shorter in the 0.3 U/kg group (all p<0.01).

In conclusion, among patients with overweight/obesity and T2D, a higher Gla-100 starting dose was as safe as a standard Gla-100 starting dose and achieved FBG targets earlier during the course of therapy.