A Randomized, Double-Blind, Placebo-Controlled Study of Gelesis100: A Novel Nonsystemic Oral Hydrogel for Weight Loss

Abstract

Objective: This study aims to assess the efficacy and safety of Gelesis100, a novel, nonsystemic, superabsorbent hydrogel to treat overweight or obesity.

Methods: The Gelesis Loss Of Weight (GLOW) study was a 24-week, multicenter, randomized, double-blind, placebo-controlled study in patients with BMI ≥ 27 and ≤ 40 kg/m² and fasting plasma glucose ≥ 90 and ≤ 145 mg/dL. The co-primary end points were placebo-adjusted weight loss (superiority and 3% margin super-superiority) and at least 35% of patients in the Gelesis100 group achieving ≥ 5% weight loss.

Results: Gelesis100 treatment caused greater weight loss over placebo (6.4% vs. 4.4%, P = 0.0007), achieving 2.1% superiority but not 3% super-superiority. Importantly, 59% of Gelesis100-treated patients achieved weight loss of ≥ 5%, and 27% achieved ≥ 10% versus 42% and 15% in the placebo group, respectively. Gelesis100-treated patients had twice the odds of achieving ≥ 5% and ≥ 10% weight loss versus placebo (adjusted OR: 2.0, P = 0.0008; OR: 2.1, P = 0.0107, respectively), with 5% responders having a mean weight loss of 10.2%. Patients with prediabetes or drug-naive type 2 diabetes had six times the odds of achieving ≥ 10% weight loss. Gelesis100 treatment had no apparent increased safety risks.

Conclusions: Gelesis100 is a promising new nonsystemic therapy for overweight and obesity with a highly desirable safety and tolerability profile.

Trial registration: ClinicalTrials.gov NCT03008954.

Figure 1

Patient disposition. GLOW, Gelesis Loss Of Weight; EX, extension; ITT, intention‐to‐treat; PP, per‐protocol.

Figure 2

Weight loss with Gelesis100 versus placebo treatment during the GLOW study among patients in the ITT population. (A) Percent change in body weight from baseline (day 0) to day 171 (after 2 days of washout) by treatment group. Error bars represent standard error of the mean (SEM). (B) Percent responders with ≥ 5% (P = 0.0008), ≥ 7.5% (P = 0.0017), or ≥ 10% (P = 0.0107) weight loss in all patients. (C) Percent change in excess body weight from baseline (day 0) to day 171 (after 2 days of washout) by treatment group. Error bars represent SEM. (D) Adjusted odds ratio (95% confidence interval) for achieving ≥ 5% (2.0 [1.3‐3.0]), ≥ 7.5% (2.1 [1.3‐3.3]), and ≥ 10% (2.1 [1.2‐3.8]) weight loss. *P < 0.05; **P < 0.001. All P values are from logistic regression models adjusted for baseline weight and stratification factors. GLOW, Gelesis Loss Of Weight; ITT, intention‐to‐treat.

Figure 3

Weight loss with Gelesis100 versus placebo treatment during the GLOW study among completers. (A) Percent responders with ≥ 5% (Gelesis100, n = 74; placebo, n = 42; P = 0.0079), ≥ 7.5% (Gelesis100, n = 49; placebo, n = 49; P = 0.0726), and ≥ 10% (Gelesis100, n = 29; placebo, n = 20; P = 0.4541) weight loss in normoglycemic completers (n = 226). (B) Adjusted odds ratio (95% confidence interval) of ≥ 5% (2.1 [1.2‐3.7]), ≥ 7.5% (1.7 [1.0‐3.0]), and ≥ 10% (1.3 [0.7‐2.5]) weight loss achieved by normoglycemic completers between treatment groups. (C) Percent responders with ≥ 5% (Gelesis100, n = 23; placebo, n = 20; P = 0.1509), ≥ 7.5% (Gelesis100, n = 17; placebo, n = 9; P = 0.0272), and ≥ 10% (Gelesis100, n = 14; placebo, n = 5; P = 0.0071) weight loss in completers with prediabetes or drug‐naive T2D (n = 68). (D) Adjusted odds ratio (95% confidence interval) of ≥ 5% (2.2 [0.8‐6.4]), ≥ 7.5% (3.4 [1.2‐10.0]), and ≥ 10% (6.1 [1.6‐22.8]) weight loss achieved by completers with prediabetes or drug‐naive T2D between treatment groups. T2D, type 2 diabetes. *P < 0.05; **P < 0.01. All P values are from logistic regression models adjusted for baseline weight and stratification factors. GLOW, Gelesis Loss Of Weight.

Figure 4

Percent change from baseline in glycemic control parameters (completers with baseline FPG ≥  90 mg/dL and not treated with antidiabetes medication). Baseline FPG was 100.9 mg/dL in the Gelesis100 group and 102.5 mg/dL in the placebo group. Mean percent change (95% CI) from baseline in FPG in Gelesis100 (n = 121) and placebo (n = 111; P = 0.1872). Baseline fasting serum insulin was 11.5 mU/L in the Gelesis100 group and 12.1 mU/L in the placebo group. Mean percent change (95% CI) from baseline in fasting serum insulin in Gelesis100 (n = 120) and placebo (n = 111; P = 0.0102). Baseline HOMA‐IR was 2.9 in the Gelesis100 group and 3.2 in the placebo group. Mean percent change (95% CI) from baseline in HOMA‐IR in Gelesis100 (n = 120) and placebo (n = 111; P = 0.0080). *P < 0.05; **P < 0.01. FPG, fasting plasma glucose; HOMA‐IR, homeostasis model assessment‐insulin resistance.