Once-Monthly Maintenance Claim Leads Data With No Verifiable Differentiation Yet

Gan & Lee Reports Phase IIIb Success in Obesity Weight Loss Maintenance

Gan & Lee has announced Phase IIIb results for its once-monthly obesity treatment, claiming to be the first to deliver such data in the maintenance setting. The drug aims to help patients maintain weight loss. GlobalData analyst Shehroz Mahmood highlighted that the maintenance aspect is becoming a key competitive area within the obesity treatment landscape, underscoring the significance of Gan & Lee's reported findings.

• Gan & Lee asserts its position as the pioneer in presenting Phase IIIb results for a once-monthly obesity treatment specifically designed for weight loss maintenance, marking a significant development in the therapeutic area.
• The press release emphasizes the drug's primary objective: to effectively maintain weight loss in patients, addressing a critical need in long-term obesity management beyond initial weight reduction.
• GlobalData analyst Shehroz Mahmood provides industry context, noting that the maintenance of weight loss is rapidly evolving into a highly competitive and crucial battleground within the broader obesity treatment market.

The Ongoing Battle for Sustained Weight Loss in Obesity

Obesity is a chronic, progressive, and relapsing disease that requires long-term, multidisciplinary management rather than episodic weight-loss treatment. Despite diet, exercise, pharmacotherapy, and bariatric surgery each producing weight loss, few subjects maintain a reduced weight over the long term and weight regain is normative.

• Marked interindividual variability in treatment response: Individual weight loss in response to diet, exercise, bariatric surgery, and medications is highly variable. Well-recognized factors associated with weight loss capacity include diet adherence, physical activity, sex, age, and specific medications, with persistent differences after control for each of these involving genetic factors, neurohormonal mechanisms including gastrointestinal peptides, metabolic efficiency and capacity of tissues, non-exercise activity thermogenesis, thermogenic response to food, and gut microbiome. Early on-treatment weight change, usually assessed within 12-16 weeks and in some liraglutide studies as early as 1 month, is the most clinically actionable predictor of longer-term outcomes.

• Rapid weight regain after cessation and need for sustained adherence: Weight regain is generally the rule, with one-third to two-thirds of the weight lost being regained within 1 year and almost all regained within 5 years. Cessation of time-restricted feeding and exercise leads to rapid weight regain, impaired glycemic control, and increased circulating lipid levels, and weight regain is particularly consistent after treatment discontinuation of GLP-1 receptor agonists and dual incretin agonists. After 2 years, lifestyle interventions can facilitate weight loss that equates to ~5%, and although 10-year percentage excess weight loss can surpass 50% after bariatric surgery, weight regain is likely.

• Pharmacotherapy tolerability, persistence, and access barriers: Real-world effectiveness of GLP-1 receptor agonists and dual incretin agonists is limited by gastrointestinal intolerance, incomplete dose escalation, cost and access barriers, poor long-term persistence, and weight plateau or regain in a subset of treated patients. Gastrointestinal adverse events were common with nausea 14.7-62%, vomiting 3-30.3%, diarrhoea 5-34.9%, while serious events, pancreatitis, and gallbladder complications were rare, with treatment discontinuation generally <15%. Pharmacological efficacy may be further limited by reductions in lean mass and inadequate nutritional intake.

• Surgical risks and long-term nutritional complications: Bariatric surgery carries well-documented risks such as gastric strictures, anastomotic leaks, thromboembolic events, infections, and the need for reoperations, with long-term challenges including nutritional deficiencies, GI complications, postoperative hypoglycaemia, and partial weight regain. Vitamin B12 deficiency was significantly more common in the Roux-en-Y gastric bypass group than sleeve gastrectomy group at 6 months: 17.46% vs. 4.69%, p < 0.001 and at 12 months: 16.74% vs. 0.93%, p < 0.001, with vitamin D deficiency prevalent and hemoglobin and ferritin levels consistently higher in the sleeve gastrectomy group.

• Lifestyle adherence and physiological adaptation: Long-term adherence to diet and exercise is challenging, with compensatory behaviors, sex differences, individual variability, and adaptation of resting metabolic rate underlying failed weight maintenance. Exercise should be increased gradually to reduce injury with a goal of 200-300 min (approximately 3.3-5 h) of moderate to vigorous intensity exercise per week to maximize weight maintenance effects, yet adopting and maintaining a high level of exercise is challenging.

Gan & Lee's Once-Monthly Therapy Shows Promise in Maintenance

Recent studies in adults with overweight or obesity evaluate once-weekly incretin-based therapies including semaglutide 2.4 mg and tirzepatide. Efficacy is reported as percentage and absolute weight change and proportions achieving threshold weight loss, while tolerability is dominated by gastrointestinal events.

Reshaping the Obesity Treatment Landscape with Novel Maintenance Strategies

Incretin-based pharmacotherapy has transitioned from DPP-4 inhibitors with modest glycaemic benefits to GLP-1 receptor agonists such as liraglutide and semaglutide with significant weight loss and cardiometabolic protection, and to next-generation dual and triple agonists. Tirzepatide, the first dual GLP-1/glucose-dependent insulinotropic polypeptide receptor agonist approved for both obesity and type 2 diabetes, paved the way for triple agonists targeting GLP-1, GIP, and glucagon receptors. In phase 2 data, retatrutide achieved up to 24.2% mean weight loss after 48 weeks in individuals with obesity and 16.9% in those with type 2 diabetes after 36 weeks, with HbA1c improved by 2.2% and 82% of participants reaching HbA1c ≤6.5%, alongside improvements in blood pressure, lipids, waist circumference, and liver fat with 82% reduction in hepatic steatosis. Across 10 randomized controlled trials including 3236 participants, incretin polyagonists reduced body weight compared to placebo (MD -11.47; 95% CI: -14.00 to -8.95), waist circumference (MD -9.40; 95% CI: -11.91 to -6.89), glycated hemoglobin (MD -0.96; 95% CI: -1.16 to -0.75), and fasting plasma glucose (MD -26.89 mg/dL; 95% CI: -33.48 to -20.30). The STEP trials showed up to 20% weight loss with semaglutide, while oral semaglutide 25 mg once daily produced an estimated mean change of -13.6% versus -2.2% with placebo (estimated difference, -11.4 percentage points; 95% confidence interval, -13.9 to -9.0; P<0.001), and once-daily oral orforglipron was associated with -48.6% to -59.4% versus -10.5% relative reduction in predicted type 2 diabetes risk at 72 weeks in ATTAIN-1.

Bariatric and metabolic surgery remains the most effective intervention for sustained weight reduction and type 2 diabetes remission when compared head-to-head with incretin therapies. In a systematic review of 14 studies (eight RCTs, six matched cohorts; N=25,566), surgery achieved superior type 2 diabetes remission (23-70% vs. 0%), greater sustained five-year weight loss (25-32% vs. 14.9-20.9% with semaglutide/tirzepatide, with significant pharmacological weight regain upon discontinuation), and lower major adverse cardiovascular events risk (pooled RR 0.48, 95% CI 0.33-0.72 vs. GLP-1 RAs; P<0.001), with superiority for non-alcoholic steatohepatitis histological resolution (56-70% vs. 59% with semaglutide). Roux-en-Y gastric bypass demonstrated higher type 2 diabetes remission than sleeve gastrectomy at 1 year (156/276, 57% versus 128/275, 47%), RR 1.20 (1.00-1.45), P = .047, with no difference in studies with 2- to 5-year follow-up, RR 1.06 (0.94-1.20), P = .34. At 1-year postsurgery in 7804 patients, significant decreases were observed in systolic blood pressure (10.5 [95% confidence interval: 10.1, 10.9] mmHg), total cholesterol (13.5 [10.3, 16.7] mg/dL), glucose (13.6 [12.9, 14.4] mg/dL), hemoglobin A1c (1.13% [1.06, 1.20]), and 10-year atherosclerotic cardiovascular disease risk (absolute reduction: 1.58% [1.22, 1.94]; relative reduction: 34.4% [29.4, 39.3]).

Real-world and maintenance data show complementary patterns of effectiveness, tolerability, and treatment persistence. In a single-center retrospective study in adults with overweight or obesity without diabetes treated for at least 36 weeks, all three treatments were associated with significant reductions in body weight and waist circumference at week 36 (p < 0.01), with greater weight loss and greater triglyceride reduction in the tirzepatide group compared with liraglutide and semaglutide groups, gastrointestinal adverse events common particularly with liraglutide, and no clinically confirmed pancreatitis observed. In 34 patients with recurrent weight gain after bariatric surgery (n = 32) or endoscopic bariatric therapy (n = 2), once-weekly subcutaneous tirzepatide (dosing range 2.5-10 mg/week) was associated with mean percentage total body weight loss of 18.1 ± 5.6% (p < 0.0001) at 24 weeks with adverse events exclusively gastrointestinal and no treatment discontinuation. Durability remains dependent on continuation: in SURMOUNT-4, withdrawing tirzepatide after 36 weeks led to 25% or greater weight regain in most participants within 1 year with greater reversal of initial cardiometabolic parameter improvements, while in 125,474 adults newly initiating liraglutide, semaglutide, or tirzepatide, 1-year discontinuation was 64.8% [95% CI, 64.4%-65.2%] without type 2 diabetes compared with 46.5% [95% CI, 46.2%-46.9%] with type 2 diabetes.