Lilly-Hims Telehealth Shifts to Approved Incretins but Persistence Risk Persists

Eli Lilly Partners with Hims & Hers for Obesity Drug Access

Eli Lilly has announced a partnership with Hims & Hers to offer its FDA-approved obesity drugs, Zepbound and Foundayo, through Hims & Hers’ telehealth platform. This collaboration allows eligible patients with a prescription to access Lilly’s medications at the same self-pay prices available elsewhere, with Foundayo starting at $149 per month and Zepbound at $299 per month. This move aligns with Hims & Hers' recent strategic shift, initiated in March after a legal challenge from Novo, to provide access to FDA-approved weight loss medicines rather than compounded versions.

• Eli Lilly is leveraging Hims & Hers' telehealth platform to broaden patient access to its FDA-approved obesity treatments, Zepbound and Foundayo. This partnership ensures that patients with valid prescriptions can obtain these medications through a convenient digital channel, maintaining the existing self-pay pricing structure.
• The agreement specifies the initial self-pay prices for Lilly's drugs, with Foundayo available at $149 per month and Zepbound starting at $299 per month. These figures provide transparency for consumers seeking access to these popular GLP-1 weight loss therapies through the Hims & Hers platform.
• This collaboration marks a significant step in Hims & Hers' revised strategy, which began in March following a legal challenge from Novo. The company has shifted its focus from offering lower-cost, compounded GLP-1 drugs to providing access to a wider array of FDA-approved weight loss medicines, reinforcing its commitment to regulated pharmaceutical options.

Navigating the Evolving Obesity Treatment Landscape with GLP-1s

Injectable glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) have redefined expectations for medical obesity therapy, with semaglutide 2.4 mg once weekly resulting in 15-17% mean weight loss and tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist, leading to up to 22.5% weight loss in phase 3 obesity trials. Published trial data report dose-dependent weight loss of semaglutide 2.4 mg/wk. -14.9% to -15.2% and tirzepatide 15-18.5%, with dual GIP/GLP-1 therapy up to 21.5%, alongside HbA1c reductions up to -1.78%, systolic blood pressure reductions of -5.28 to -7.8 mmHg, and LDL-C decreases up to -11 mg/dL. In a network meta-analysis of 28 randomized controlled trials comprising 34,367 participants, tirzepatide demonstrated superiority over semaglutide in percentage weight reduction (mean difference [MD] 6.10%; 95% CI: 3.64, 8.57), absolute weight loss (MD 4.55 kg; 95% CI: 1.28, 7.83), BMI reduction (MD 1.71 kg/m; 95% CI: 0.08, 3.34), waist circumference reduction (MD 2.89 cm; 95% CI: 1.25, 4.53), HbA1c reduction (MD 0.33%; 95% CI: 0.20, 0.46) and fasting blood glucose reduction (MD 10.39 mg/dL; 95% CI: 4.48, 16.29).

The pipeline has expanded beyond single-pathway GLP-1RAs to engineered dual and triple peptide-based co-agonists combining GLP-1 with GIP, glucagon, amylin, or peptide YY. Retatrutide, a GLP1R/GCGR/GIPR tri-agonist, has been associated with a placebo-subtracted weight reduction of -22.1% in a 48-week phase-II trial, with triple agonists such as retatrutide achieving weight reductions of 20-24% in clinical studies. In a network meta-analysis of 25 trials involving 12 interventions, tirzepatide 15 mg resulted in the greatest percent weight reduction (MD -17.97%), followed by CagriSema (MD -17.84%) and semaglutide 7.2 mg (MD -14.66%), while at the ≥20% weight-loss threshold, CagriSema demonstrated marked superiority (RR 27.82), followed by tirzepatide 15 mg (RR 23.70). Dual GLP-1/glucagon agonists like survodutide and mazdutide show strong efficacy with particular promise for metabolic-associated steatotic liver disease, Maridebart cafraglutide, combining GLP-1 agonism with glucose-dependent insulinotropic polypeptide (GIP) antagonism, enables once-monthly dosing, and the amylin pathway has re-emerged through long-acting analogs (cagrilintide, eloralintide) and unimolecular co-agonists (amycretin), achieving weight reductions up to 24% via distinct neuroendocrine circuits, while body composition optimization through agents like bimagrumab addresses lean mass preservation during potent anorectic therapy.

Oral GLP-1 therapies have entered the obesity arena as non-peptidyl and peptide formulation strategies to enhance treatment accessibility and adherence. ATTAIN-1 evaluated orforglipron in 3,127 adults with obesity over 72 weeks, demonstrating a mean weight loss of 11.2%, ≥ 10% weight loss in 54.6%, and improvements in cardiometabolic parameters, while OASIS-4 studied oral semaglutide 25 mg in 307 adults over 64 weeks, showing a mean weight loss of 13.6%, ≥ 10% weight loss in 63%, and favorable metabolic changes. Orforglipron, a novel oral non-peptide GLP-1 receptor agonist, demonstrated dose-dependent reductions in body weight from 2.48% at 3 mg to 9.8% at 45 mg, BMI from 0.89 to 3.62 kg/m, waist circumference from 1.57 to 6.9 cm, and HbA1c from 0.76% to 1.04% compared with placebo, with reductions in total cholesterol (MD: -4.51% [95% CI: -6.91 to -2.11]), LDL-C (MD: -5.34% [95% CI: -7.10 to -3.58]), and triglycerides (MD: -10.07% [95% CI: -12.33 to -7.80]). Both oral agents exhibited gastrointestinal adverse events consistent with the GLP-1 class, with gastrointestinal adverse events significantly more frequent at orforglipron doses of 12 mg or higher, and serious adverse events and mortality rates comparable to those with placebo.

Addressing Unmet Needs in Obesity Treatment Through Strategic Partnerships

Real-world effectiveness in obesity is determined not only by biological efficacy but also by treatment tolerability, adherence, access and sustained support. Despite long-term weight loss and metabolic improvement with current options, attrition, weight regain, adverse effects and inequitable access continue to attenuate outcomes in practice.

• Lifestyle modification shows limited durability and adherence challenges. Intensive lifestyle interventions generally achieve approximately 5% weight loss, but attrition and weight regain after programme completion are common. Randomized, controlled trials show only modest weight loss with exercise intervention alone, and long-term adherence to exercise was problematic, with weight regain being normative.

• Pharmacotherapy is limited by tolerability, persistence and access barriers. Incretin-based therapies, including semaglutide and tirzepatide, produce substantial weight loss in trials but real-world effectiveness is relatively smaller because of non-initiation, incomplete dose escalation, gastrointestinal adverse effects, treatment interruptions, and financial or insurance barriers. Older medications demonstrate poor persistence, largely related to neurologic, psychiatric or gastrointestinal intolerance, while earlier agents such as fenfluramine, sibutramine, and orlistat fell short due to limited effectiveness, serious side effects including valvular heart disease and gastrointestinal issues, and high rates of treatment discontinuation. High costs, supply shortages, and unequal access pose significant barriers, with gastrointestinal side effects and long-term safety concerns requiring close monitoring, and weight regain after medication discontinuation emphasizing the need for ongoing adherence and lifestyle support.

• Metabolic bariatric surgery provides the greatest weight loss but remains underused and carries surgical and nutritional risks. MBS provides the greatest and most durable weight loss but remains substantially underused, with racial, socioeconomic and insurance disparities. Surgery is associated with complications, such as pulmonary embolism, and some postoperative deaths occurred, with mortality within 30 days of surgery higher than in nonsurgically treated controls (1.55% vs 0.53%; P < .001). Compared with sleeve gastrectomy and adjustable gastric banding, Roux-en-Y gastric bypass appears to be associated with greater weight loss but major and/or serious complications are more common after RYGB, with less incidence of dumping syndrome reported for vertical sleeve gastrectomy.

• Nutritional deficiencies are enduring metabolic complications of surgery. Most studies of vitamin D status in bariatric surgery candidates reported a prevalence of over 50% vitamin D deficiency (<50 nmol/L), enduring post-operatively with one study reporting 65% deficient at 10 years post-bariatric surgery. Vitamin B12 deficiency was significantly more common in the RYGB group (6 months: 17.46% vs. 4.69%, p < 0.001; 12 months: 16.74% vs. 0.93%, p < 0.001), with vitamin B12, hemoglobin, and ferritin levels consistently higher in the SG group.

• Endoscopic options and physiology further constrain durability. Endoscopic sleeve gastroplasty offers moderate, durable weight loss with low serious adverse event rates, whereas intragastric balloons are more limited by intolerance, reintervention and weight regain after removal. Physiological adaptations to weight loss favour weight regain, including perturbations in the levels of circulating appetite-related hormones and energy homoeostasis, in addition to alterations in nutrient metabolism and subjective appetite.