Projections from the World Obesity Federation estimate that the number of adults living with obesity will rise from 810 million in 2020 to 1.53 billion by 2035.

Among the strategies to address this challenge are anti-obesity medications such as sibutramine and topiramate. The combination of these two drugs has been used off-label in clinical practice. Until recently, however, data on the efficacy and safety profile of this therapy were limited.

The SIBAMATE study, published in the July issue of Diabetology & Metabolic Syndrome, is beginning to change that picture.

Study Details

Researchers at the Hospital das Clínicas, University of São Paulo Medical School (HCFMUSP), São Paulo, Brazil, conducted the retrospective SIBAMATE study with 246 patients. All participants were 18 years or older with a BMI > 30 or a BMI > 27 with at least one comorbidity (type 2 diabetes, hypertension, or dyslipidemia).

Women accounted for the majority (86.2%), with a mean age of 42.8 years. Comorbidities included hypertension (52%), type 2 diabetes (31.3%), and dyslipidemia (30%). At baseline, the mean BMI was 39.7, and mean weight was 104.2 kg.

All patients received the sibutramine-topiramate combination for at least 3 months. They also received counseling on a hypocaloric diet, were encouraged to engage in regular physical activity, and were monitored by a multidisciplinary team of endocrinologists and nutritionists.

Weight Loss Maintained Over Time

The mean daily doses were 11 ± 2.1 mg of sibutramine and 119.7 ± 54.7 mg of topiramate. At 3 months of therapy, weight loss was significant: 61.8% of patients lost > 5% of body weight, 29.4% lost > 10%, and 10.9% lost > 15%. At 36 months, 64% maintained ≥5% weight loss, 40.6% maintained ≥10%, and 26.5% maintained ≥15%.

Speaking with Medscape’s Portuguese edition, Matheo Augusto Stumpf, endocrinologist and metabolic specialist, PhD candidate at HCFMUSP, and one of the study authors, said the results were not surprising as sibutramine acts similarly to phentermine, another anti-obesity agent.

While no prior studies had assessed sibutramine-topiramate directly, evidence already exists for the phentermine-topiramate combination (marketed as Qsymia). “Pivotal trials such as CONQUER and EQUIP, focused on weight loss, demonstrated that phentermine-topiramate was safe and effective, with average weight loss of 8%-10%,” Stumpf noted.

Phentermine-topiramate has been approved in the US since 2012, but phentermine is not available in Brazil. According to Stumpf, one reason Brazil’s regulatory agency, ANVISA, has not approved the combination is the absence of cardiovascular safety studies.

Attention to Contraindications

The SIBAMATE study also found sibutramine-topiramate to be generally well tolerated. Reported side effects included paresthesia, memory impairment, bradyphrenia, and elevated blood pressure.

Marcio Mancini, endocrinologist, director of the Department of Pharmacological Treatment at the Brazilian Association for the Study of Obesity and Metabolic Syndrome (ABESO), member of the Brazilian Society of Endocrinology and Metabolism (SBEM), and another study author, observed that side effects often offset one another. “Sibutramine is mildly stimulating, while topiramate slows things down. So the combination enhances weight loss while reducing adverse effects,” he told Medscape’s Portuguese edition.

Still, 60 patients (24.4%) discontinued therapy, mainly because of uncontrolled hypertension (4.9%), refractory paresthesia (3.2%), and tachycardia (2.8%).

Stumpf suggested strategies to reduce discontinuation, such as slower dose titration. “For patients who develop hypertension or tachycardia, antihypertensives and beta blockers can be prescribed to improve tolerance and avoid premature discontinuation,” he advised.

He emphasized, however, that careful patient selection is critical. The combination should be avoided in patients with uncontrolled hypertension, arrhythmias, or very high cardiovascular risk.

Mancini added that sibutramine is contraindicated in patients with coronary artery disease, prior stroke, multiple risk factors for coronary disease, and those older than 65 years. Topiramate is contraindicated in patients with angle-closure glaucoma. It may also increase the risk for kidney stones and cognitive and memory impairment and is teratogenic. “It should be used with great caution in women of childbearing age, ensuring dual contraception,” he said.

Broader Medical Perspectives

Other specialists also weighed in. Alexandre Hohl, director of ABESO and of the Department of Female Endocrinology, Andrology, and Transgender Medicine at SBEM, told Medscape’s Portuguese edition that sibutramine is labeled for obesity treatment, while topiramate is part of the therapeutic arsenal when binge eating is a concern. “So the combination makes sense pharmacologically, and this study reflects what is already being done in clinical practice,” he said.

According to Hohl, the combination is feasible, particularly at the doses tested in SIBAMATE, which have been shown to be safe. He described it as “useful for weight loss in people who benefit from reduced hunger and satiety signals, as well as improvement in binge eating.”

He also pointed out that sibutramine has been withdrawn from the market in several countries, but Brazil remains one of the few where it is still available. Its main advantage is affordability. “We may be the country with the most experience using this drug combination for obesity,” he noted.

Carolina Castro Porto Silva Janovsky, endocrinologist, professor of clinical endocrinology at the Federal University of São Paulo and its Escola Paulista de Medicina (Paulista School of Medicine), and SBEM member, also prescribes the sibutramine-topiramate combination in her practice. She told Medscape’s Portuguese edition that her real-world experience mirrors the results of SIBAMATE: “In my clinic, patients who receive proper dietary and exercise counseling, along with multidisciplinary support, achieve significant weight loss — and, most importantly, maintain it for many months.”

For her, the therapy is particularly valuable for Brazilian patients given its efficacy, affordability, and regulatory context. “In Brazil, GLP-1 receptor agonists such as semaglutide and tirzepatide are not available through SUS [public health system], and their private-market prices are high,” she explained.

She added that the therapy’s tolerability profile is another advantage but emphasized the importance of systematic monitoring of blood pressure, cognition, and mood, with dose adjustments or discontinuation as needed. “It is clearly a second-line option for patients who lack access to newer agents or who do not respond adequately to lifestyle modification alone,” she said.

This story was translated from Medscape’s Portuguese edition.