Obesity (Silver Spring)Weight LossCohortDecember 26, 2025

Weight Loss With SGLT2 Inhibitors, Semaglutide, and Transcranial Magnetic Stimulation in Type 2 Diabetes and Obesity.

Ferrulli A, Senesi P, Sonaglioni A, Cannavaro D, Massarini S, Macrì C, Cipponeri E, DeFronzo RA, Luzi L

Key Finding

Brain stimulation therapy (rTMS) produced weight loss of 8.2 kg after one year, matching semaglutide's 5.7 kg loss and dramatically outperforming SGLT2 inhibitors' modest 2.0 kg loss in people with diabetes and obesity.

What This Study Found

Think of this study like comparing three different routes to the same mountain summit - weight loss for people with both diabetes and obesity. Researchers followed 107 patients for a full year, giving them one of three treatments: brain stimulation (rTMS - like a magnetic 'tune-up' for appetite control centers), semaglutide injections (the diabetes/weight loss drug), or SGLT2 inhibitors (diabetes pills that make you pee out sugar). The brain stimulation group got 15 sessions over 5 weeks - imagine targeted magnetic pulses rewiring how their brain responds to food cravings. All groups also cut 300 calories daily from their diet. The results were striking: rTMS delivered the biggest punch with 8.2 kg lost, semaglutide came in second at 5.7 kg, while SGLT2 inhibitors managed only 2.0 kg - like comparing a sports car, sedan, and bicycle in a race. Most tellingly, people taking SGLT2 pills actually started gaining weight back after 6 months, while the other two groups kept losing steadily, suggesting more durable appetite control.

Statistics Decoded

The p-values tell us these differences weren't just luck: p = 0.01 for semaglutide vs SGLT2i means there's only a 1-in-100 chance this difference happened by coincidence, while p < 0.0001 for rTMS vs SGLT2i means less than 1-in-10,000 chance of being random - like flipping heads 13+ times in a row. The weight losses translate to: rTMS achieved about 8-10% body weight reduction, semaglutide about 5-7%, and SGLT2i only 2-3% in typical patients. The ± numbers show the variability - most rTMS patients lost between 7.2-9.2 kg, while semaglutide patients lost 4.8-6.6 kg.

Why This Matters

This opens a potentially game-changing non-drug option for weight loss that rivals expensive GLP-1 medications - especially important since many insurance plans don't cover weight loss drugs, and rTMS could offer a one-time treatment course rather than lifelong injections.

Original Abstract

This study compared the efficacy of a GLP-1 receptor agonist (GLP1-RA) (semaglutide, 0.5 mg/week), sodium-glucose cotransporter-2 inhibitors (SGLT2i), and repetitive transcranial magnetic stimulation (rTMS), a new emerging treatment for obesity, in reducing body weight (BW) after 1 year in patients with obesity and type 2 diabetes (T2D). We included 40 patients with T2D treated with a SGLT2i, 37 patients with T2D treated with the GLP1-RA semaglutide, and 30 patients treated with rTMS in this retrospective comparative analysis. rTMS was administered three times per week for 5 weeks. All patients received dietary advice about moderate caloric restriction (-300 kcal/day). After 12 months the weight loss with rTMS (-8.2 ± 1.0 kg) was not significantly different from that with semaglutide (-5.7 ± 0.9 kg). Weight loss with SGLT2i (-2.0 ± 0.7 kg) was significantly less than with both semaglutide (p = 0.01) and rTMS (p < 0.0001). Individuals receiving SGLT2i therapy experienced weight regain from month 6 to month 12, while BW declined progressively in patients treated with semaglutide and rTMS. Treatment with rTMS produced a comparable reduction in BW to that observed with the GLP1-RA semaglutide (at the dose of 0.5 mg/week) and represents a promising intervention for the treatment of obesity and T2D. ClinicalTrials.gov identifier: NCT03009695.