Coadministration of Canagliflozin and Phentermine for Weight Management in Overweight and Obese Individuals Without Diabetes: A Randomized Clinical Trial

Hollander, Priscilla; Bays, Harold; Rosenstock, Julio; Frustaci, Mary Ellen; Fung, Albert; Vercruysse, Frank; Erondu, Ngozi

doi:10.2337/dc16-2427

Cited by 89 publications

(86 citation statements)

References 28 publications

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“…Despite the observed maintenance of weight loss in patients with T2DM treated with SGLT2 inhibitors, the observed reduction in body weight tends to plateau after approximately 26 weeks despite sustained urinary glucose excretion, with observed weight loss less than predicted based on caloric loss from urinary glucose excretion (34,35). Factors including compensatory increases in calorie intake and/or changes in energy expenditure may contribute to this attenuated weight loss.…”

Section: Discussionmentioning

confidence: 93%

“…In a recent meta‐analysis, body weight significantly decreased in patients with T2DM who received different dosages of SGLT2 inhibitors (dapagliflozin, empagliflozin, canagliflozin, ipragliflozin, tofogliflozin, and luseogliflozin) compared with patients who received a placebo, with a greater reduction in body weight with higher doses of SGLT2 inhibitors . Despite the observed maintenance of weight loss in patients with T2DM treated with SGLT2 inhibitors, the observed reduction in body weight tends to plateau after approximately 26 weeks despite sustained urinary glucose excretion, with observed weight loss less than predicted based on caloric loss from urinary glucose excretion . Factors including compensatory increases in calorie intake and/or changes in energy expenditure may contribute to this attenuated weight loss.…”

Section: Discussionmentioning

confidence: 98%

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Efficacy and Safety of Ertugliflozin in Patients with Overweight and Obesity with Type 2 Diabetes Mellitus

Heymsfield

Raji

Gallo

et al. 2020

Obesity

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Objective This study aimed to evaluate ertugliflozin in patients with overweight and obesity with type 2 diabetes mellitus. Methods Data from three placebo‐controlled, randomized, Phase 3 studies were pooled. Patients with baseline BMI ≥ 25 (1,377/1,544; 89%) were assessed with a stratification by BMI subgroup. Results At week 26, reductions from baseline in glycated hemoglobin A1c (HbA1c), fasting plasma glucose, body weight (BW), and systolic blood pressure (SBP) were greater with ertugliflozin versus placebo. For placebo, ertugliflozin 5 mg, and ertugliflozin 15 mg, respectively, least squares mean change was 0.1%, −0.8%, and −0.9% for HbA1c and −1.2 kg, −3.1 kg, and −3.2 kg for BW. HbA1c reductions were consistent across BMI subgroups. For ertugliflozin 5 mg and 15 mg, least squares mean change (placebo adjusted) in absolute BW was −1.4 kg and −1.2 kg for BMI 25 to < 30, −1.8 kg and −1.9 kg for BMI 30 to < 35, and −2.5 kg and −2.9 kg for BMI ≥ 35. Percent BW changes were similar across BMI subgroups. Incidence of adverse events was 52.5%, 44.6%, and 50.1% with placebo, ertugliflozin 5 mg, and ertugliflozin 15 mg, respectively. Conclusions Meaningful reductions in HbA1c, fasting plasma glucose, BW, and SBP were observed with ertugliflozin in patients with overweight and obesity with type 2 diabetes mellitus. Ertugliflozin improved HbA1c and SBP and reduced BW across BMI subgroups. Ertugliflozin was generally well tolerated.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 98%

Efficacy and Safety of Ertugliflozin in Patients with Overweight and Obesity with Type 2 Diabetes Mellitus

Heymsfield

Raji

Gallo

et al. 2020

Obesity

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“…Subsequently, a further trial investigated the co-administration of canagliflozin and phentermine in obese patients without T2D. Over 26 weeks, participants using canagliflozin lost 1.9 kg compared with 4.1 kg in those using phentermine and 7.3 kg in participants using both drugs [70].…”

Section: Canagliflozinmentioning

confidence: 99%

Drug Therapy in Obesity: A Review of Current and Emerging Treatments

2020

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Whilst the prevalence of obesity continues to increase at an alarming rate worldwide, the personal and economic burden of obesity-related complications becomes ever more important. Whilst dietary and lifestyle measures remain the fundamental focus of the patient to counter obesity, more frequently pharmacological and/or surgical interventions are required. Nevertheless, these therapies are often limited by weight loss efficacy, side effects, surgical risks and frequently obesity relapse. Currently, only five drug therapies are approved for the specific treatment of obesity. However, our understanding of the pathophysiology of obesity and of gut hormones has developed precipitously over the last 20-30 years. As a result, there has been a recent movement to create and use analogues that manipulate these gut hormones to support weight loss. In this article we review the efficacy of the currently approved drug therapies and discuss future potential drug mechanisms and early clinical trial results exploring these budding avenues. We discuss the use of glucagon-like peptide-1 (GLP-1) analogues as monotherapy and unimolecular dual or triple agonists that exploit the GLP-1 receptor and/or the gastric inhibitory peptide (GIP) receptor and/or the glucagon receptor. We also explore the use of sodiumglucose co-transporter-2 (SGLT-2) inhibitors, amylin mimetics, leptin analogues, ghrelin antagonists and centrally acting agents to suppress appetite [neuropeptide Y (NPY) antagonists, melanocortin-4 receptor (MC4R) agonists and cannabinoid-1 receptor antagonists]. Whilst further evidence is required to support their clinical use, preclinical and early clinical trial results are encouraging. Key Summary PointsObesity is a complex metabolic disorder, with several licensed drug and surgical therapies currently available.Current therapies are often associated with inadequate efficacy or complications and side effects, limiting their use.Multiple pathophysiological mechanisms of obesity are recognized, though only few of these are manipulated using currently licensed therapies.Whilst most drug classes are in early stages of development and/or clinical trials, results are promising for multiple drug targets.

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“…SGLT2 inhibitors in combination with GLP‐1RAs have emerged as a potential treatment for T2D in adults, with weight loss considerably more pronounced than that achieved with either pharmacotherapy agent alone . Additionally, SGLT2 inhibitors in combination with phentermine have been shown to have synergistic weight loss effects in adults without diabetes (∼7% BMI reduction, placebo subtracted) . If SGLT2 inhibitors prove to be safe and effective in children, the next logical step may be to evaluate the combination of this class of medication with GLP‐1RAs or with stimulants, like phentermine.…”

Section: The Future Of Pediatric Severe Obesity Treatmentmentioning

confidence: 99%

Treatment Options for Severe Obesity in the Pediatric Population: Current Limitations and Future Opportunities

Ryder

Fox

Kelly

2018

Obesity

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Coadministration of Canagliflozin and Phentermine for Weight Management in Overweight and Obese Individuals Without Diabetes: A Randomized Clinical Trial

Abstract: CANA/PHEN produced meaningful reductions in body weight and was generally well tolerated in individuals who were overweight or obese without type 2 diabetes. Further studies are warranted to evaluate potential use of this combination for long-term weight management.

Cited by 89 publications

References 28 publications

Efficacy and Safety of Ertugliflozin in Patients with Overweight and Obesity with Type 2 Diabetes Mellitus

Efficacy and Safety of Ertugliflozin in Patients with Overweight and Obesity with Type 2 Diabetes Mellitus

Drug Therapy in Obesity: A Review of Current and Emerging Treatments

Treatment Options for Severe Obesity in the Pediatric Population: Current Limitations and Future Opportunities

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