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Phentermine/Topiramate Slows Progression to T2DM

Cardiometabolic risk factors also significantly improved….

Weight loss of 5-10% of one’s total body weight has been shown to be effective in preventing progression to diabetes in patients who are obese or overweight. Sustained weight loss is easier said than done, though, with many patients struggling to change their lifestyle habits. Phentermine and topiramate ER have already been shown to produce significant weight loss when combined with lifestyle modifications in overweight and obese patients, though less is known about their ability to reduce progression to T2DM in at risk individuals. Garvey, WT et al. conducted a study to assess the effect of PHEN/TPM ER treatment on progression to T2DM and/or cardiometabolic disease in patients who have prediabetes and/or metabolic syndrome at baseline.

Data for this study was obtained from the SEQUEL study, a 52-week extension study of the CONQUER study, which assessed the effectiveness of PHEN/TPM ER for weight loss in overweight and obese adults (BMI≥27 to ≤45 kg/m2) with 2 or more comorbidities. The study followed the participants for a total of 108 weeks, with 475 patients meeting the criteria for prediabetes and/or metabolic syndrome at baseline. Subjects were randomized to three different groups: placebo, PHEN 7.5mg/TPM ER 46mg, or PHEN 15mg/TPM ER 92mg plus lifestyle modifications. Outcomes that were measured include percent weight loss, annualized incidence rate of progression to type 2 diabetes, and changes in glycemia, lipid parameters, blood pressure, and waist circumference.

Mean percent weight loss for the placebo, 7.5/46, and 15/92 groups was 2.5, 10.9, and 12.1% respectively. This weight loss was associated with a 70.5% and 78.7% reduction in the annualized incidence rate of type 2 diabetes for the 7.5/46 and 15/92 groups, respectively. The magnitude of the effect on type 2 diabetes prevention was related to the degree of weight loss that was achieved after 108 weeks, with greater weight loss being associated with a greater reduction in incidence of T2DM regardless of randomization group. Reports of adverse events showed this drug combination to be generally well tolerated, with appendicitis being the only treatment-emergent AE to cause discontinuation of the study medications in ≥1% of subjects receiving any treatment dose (2 patients in the 15/92 group). The PHEN/TPM ER groups also significantly improved cardiometabolic risk factors when compared to the placebo group, with fasting glucose, fasting insulin, 2-h post-OGTT glucose, fasting TGL’s, and HDL-C all improved after study completion.

The results of this study showed PHEN/TPM ER to be highly effective at both inducing and sustaining weight loss in overweight/obese patients with prediabetes and/or metabolic syndrome. This weight loss was in turn associated with improvements in multiple cardiometabolic disease risk factors in addition to having a profound effect on the prevention of type 2 diabetes. Additional research on the use of PHEN/TPM ER beyond two years would be beneficial, as it is important to know whether weight loss with PHEN/TPM ER and its associated protective effect against diabetes will be maintained beyond this time frame, and what the associated risks are with long term use of this drug combination. In conclusion, this data suggests that PHEN/TPM ER, in addition to lifestyle modifications, may be a new and effective approach to decrease risk of type 2 diabetes and cardiometabolic disease in obese and overweight patients with prediabetes and/or metabolic syndrome.

Practice Pearls:
  • Phentermine/topiramate ER produced significant weight loss in patients and caused a statistically significant reduction in incident rates of diabetes. Greater weight loss was found to lead to greater reductions in progression to T2DM.
  • These medications were generally well tolerated, though longer-term data is needed on the benefits and risks of prolonged use of phentermine and topiramate ER.

Garvey, WT et al. "Prevention of Type 2 Diabetes in Subjects With Prediabetes and Metabolic Syndrome Treated With Phentermine and Topiramate Extended Release" Diabetes Care. 2014; 37: 912- 921.