Multicenter, Phase 4 Clinical Study from India to Evaluate the Safety and Efficacy of Insulin Glargine 300 U/ml in Insulin-Naïve People with Type 2 Diabetes Uncontrolled on Oral Anti-hyperglycemic Drugs: SAFEGUARD Study

Abstract

Introduction: The clinical benefits of insulin glargine 300 U/ml (Gla-300) have been confirmed in randomized clinical trials (EDITION and BRIGHT) and real-world studies (ATOS, Toujeo-1, and ORION) in different regions of the world. However, safety data for the Indian population are lacking. The current post-marketing surveillance study evaluated the safety and efficacy of Gla-300 in people with type 2 diabetes (T2D) from India.

Methods: SAFEGUARD was a multicenter, phase 4, single-arm, open-label, 24-week study conducted at 15 centers across India between August 10, 2021 and December 26, 2022. The study included insulin-naïve participants (aged ≥ 18 years) with T2D uncontrolled (HbA1c ≥ 7.5% and ≤ 10%) on oral anti-hyperglycemic drugs. The primary endpoint was the percentage of participants with treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs) and hypoglycemic episodes.

Results: Of the 220 participants included, 218 (36.8% female) were eligible for efficacy analysis. The mean ± standard deviation age was 54.0 ± 9.6 years, the baseline HbA1c was 8.8 ± 0.9%, and the duration of T2D was 9.3 ± 7.0 years. Among the 220 participants who took at least one dose of Gla-300, 24.5% (n = 54) reported 64 TEAEs, which included one (0.5%) SAE. The most reported event was infections (10.9%). In total, 29.5% of participants (n = 65) reported a level 1 hypoglycemic event, and 27.7% of participants (n = 18) reported the main symptom of sweating. Glycemic control improved with reductions in mean HbA1c levels (- 1.14 ± 1.2%), fasting plasma glucose (- 37.0 ± 59.3 mg/dl), and fasting self-monitored blood glucose (- 52.0 ± 44.1 mg/dl) from baseline to week 24.

Conclusions: Gla-300 was well tolerated with improved glycemic control and a low hypoglycemia risk in insulin-naïve people with T2D living in India.

Trial registration: Clinical Trials Registry-India (CTRI number): CTRI/2021/07/035244. WHO identifier number: U1111-1255-5143. NCT number: NCT04980027.

Keywords: Diabetes mellitus; Hypoglycemia; India; Insulin glargine; SAFEGUARD.

Fig. 1

Efficacy outcomes: a change in HbA1c from baseline^a to week 12 and week 24 and b percentage of participants^b reaching the HbA1c target of < 7% (secondary endpoint) in the per-protocol population^c measured during Gla-300 treatment. Data presented as mean ± SD unless stated otherwise. ^#Efficacy analyses were undertaken in the per-protocol population. ^aBaseline was defined as the latest non-missing measurement prior to Gla-300 administration, including repeat assessments and unscheduled visits. ^bPercentages are based on the number of participants in the per-protocol population who attended the corresponding visit. ^cThe per-protocol population was defined as a subset of the participants in the safety population with no critical protocol violation. HbA1c glycated hemoglobin, N number of participants, SD standard deviation

Fig. 2

Clinical measures during Gla-300 treatment from baseline^a to weeks 12 and 24 in the pre-protocol population^b: a percentage of participants^c reaching targeted^d fasting SMBG, b change in FPG (mg/dl), c fasting SMBG (mg/dl), d change in 7-point SMPG, e mean change in body weight (kg) and f mean change in daily insulin dose^e (U). Data presented as mean ± SD unless stated otherwise. ^#Efficacy analyses were undertaken in the per-protocol population. ^aBaseline was defined as the latest non-missing measurement prior to Gla-300 administration at the respective time point. ^bThe per-protocol population was defined as a subset of the participants in the safety population with no critical protocol violation. ^cPercentages are based on the number of participants in the per-protocol population who attended the corresponding visit. ^dAverage of fasting SMBG of 80–110 mg/dl (4.4–6.1 mmol/l). ^eMean insulin dose per day (U) = Total amount of dose administered/Total days treatment administered > 0. FPG fasting plasma glucose, N number of participants, SD standard deviation, SMBG self-monitored blood glucose, SMPG self-monitoring plasma glucose

Fig. 2

Clinical measures during Gla-300 treatment from baseline^a to weeks 12 and 24 in the pre-protocol population^b: a percentage of participants^c reaching targeted^d fasting SMBG, b change in FPG (mg/dl), c fasting SMBG (mg/dl), d change in 7-point SMPG, e mean change in body weight (kg) and f mean change in daily insulin dose^e (U). Data presented as mean ± SD unless stated otherwise. ^#Efficacy analyses were undertaken in the per-protocol population. ^aBaseline was defined as the latest non-missing measurement prior to Gla-300 administration at the respective time point. ^bThe per-protocol population was defined as a subset of the participants in the safety population with no critical protocol violation. ^cPercentages are based on the number of participants in the per-protocol population who attended the corresponding visit. ^dAverage of fasting SMBG of 80–110 mg/dl (4.4–6.1 mmol/l). ^eMean insulin dose per day (U) = Total amount of dose administered/Total days treatment administered > 0. FPG fasting plasma glucose, N number of participants, SD standard deviation, SMBG self-monitored blood glucose, SMPG self-monitoring plasma glucose