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Background/Objectives: The interaction between fasting plasma glucose (FPG) and fasting insulin (FI) concentrations and diets with different carbohydrate content were studied as prognostic markers of weight loss as recent studies up to 6 months of duration have suggested the importance of these biomarkers.Subjects/Methods: This was a retrospective analysis of a clinical trial where participants with obesity were randomized to an ad libitum low-carbohydrate diet or a low-fat diet with low energy content (1200–1800 kcal/day [≈ 5.0–7.5 MJ/d]; ≤ 30% calories from fat) for 24 months. Participants were categorized (pretreatment) as normoglycemic (FPG < 5.6 mmol/L) or prediabetic (FPG ≥ 5.6–6.9 mmol/L) and further stratified by median FI. Linear mixed models were used to examine outcomes by FPG and FI values.Results: After 2 years, participants with prediabetes and high FI lost 7.2 kg (95% CI 2.1;12.2, P = 0.005) more with the low-fat than low-carbohydrate diet, whereas those with prediabetes and low FI tended to lose 6.2 kg (95% CI −0.9;13.3, P = 0.088) more on the low-carbohydrate diet than low-fat diet [mean difference: 13.3 kg (95% CI 4.6;22.0, P = 0.003)]. No differences between diets were found among participants with normoglycemia and either high or low FI (both P ≥ 0.16).Conclusions: Fasting plasma glucose and insulin are strong predictors of the weight loss response to diets with different macronutrient composition and might be a useful approach for personalized weight management.

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.

Efforts to identify a preferable diet for weight management based on macronutrient composition have largely failed, but recent evidence suggests that satiety effects of carbohydrates may depend on the individual's insulin-mediated cellular glucose uptake. Therefore, using data from the POUNDS LOST trial, pre-treatment fasting plasma glucose (FPG), fasting insulin (FI), and homeostatic model assessment of insulin resistance (HOMA-IR) were studied as prognostic markers of long-term weight loss in four diets differing in carbohydrate, fat, and protein content, while assessing the role of dietary fiber intake. Subjects with FPG <100 mg/dL lost 2.6 (95% CI 0.9;4.4, p = 0.003) kg more on the low-fat/high-protein (n = 132) compared to the low-fat/average-protein diet (n = 136). Subjects with HOMA-IR ≥4 lost 3.6 (95% CI 0.2;7.1, p = 0.038) kg more body weight on the high-fat/high-protein (n = 35) compared to high-fat/average-protein diet (n = 33). Regardless of the randomized diet, subjects with prediabetes and FI below the median lost 5.6 kg (95% CI 0.6;10.6, p = 0.030) more when consuming ≥35 g (n = 15) compared to <35 g dietary fiber/10 MJ (n = 16). Overall, subjects with normal glycemia lost most on the low-fat/high-protein diet, subjects with high HOMA-IR lost most on the high-fat/high protein diet, and subjects with prediabetes and low FI had particular benefit from dietary fiber in the diet.