Emerging Role of SGLT-2 Inhibitors for the Treatment of Obesity

Pereira, Maria J.; Eriksson, Jan W.

doi:10.1007/s40265-019-1057-0

Cited by 177 publications

(140 citation statements)

References 100 publications

Supporting

Mentioning

123

Contrasting

Unclassified

Order By: Relevance

“…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: 97%

“…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%

See 1 more Smart Citation

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

Heymsfield

Raji

Gallo

et al. 2020

Obesity

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 97%

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

View full text Add to dashboard Cite

show abstract

“…Theoretically, SGLT2i-induced urinary caloric loss can be sustained even after the improvement of glycemic control. Additionally, SGLT2i-induced weight loss is sustained because the SGLT2i can continue to accelerate the excretion of glucose into the urine in patients without T2DM [9,16]. In most patients, however, the amount of SGLT2i-induced weight loss is approximately 2 kg to 3 kg, and this weight loss plateaus within six months [17][18].…”

Section: Discussionmentioning

confidence: 99%

“…This results in the metabolism of the accumulated fat and a reduction in body weight by loss of calories into the urine [7]. This SGLT2i-induced weight loss might be beneficial for a wide range of patients with T2DM [8][9].…”

Section: Introductionmentioning

confidence: 99%

Type 2 Diabetes Remission and Substantial Body Weight Reduction Achieved with Metformin and a Sodium-Glucose Cotransporter 2 Inhibitor

Sugiyama¹,

Jinnouchi²,

Hieshima³

et al. 2020

Cureus

View full text Add to dashboard Cite

The overall goal in the treatment of type 2 diabetes mellitus (T2DM) is remission. However, the effects of a sodium-glucose cotransporter 2 inhibitor (SGLT2i) on remission of T2DM are unknown. We herein report a case involving an overweight 43-year-old man who completely recovered from T2DM after SGLT2i therapy (dapagliflozin at 5 mg/day). In the pretreatment period, he had a body mass index (BMI) of 26.0 kg/m 2 , hemoglobin A1c (HbA1c) concentration of 10.3%, advanced insulin resistance, pancreatic β-cell dysfunction, and fatty liver. Eighteen months after comprehensive therapy, including the administration of an SGLT2i and metformin, his BMI had decreased to 21.3 kg/m 2 and his glycemic control was almost normal (HbA1c of 5.3%) despite discontinuation of all hypoglycemic medications. This report is the first to propose the usefulness of the combination therapy of SGLT2i and metformin for achieving normal body weight and remission of newly diagnosed T2DM in a real-world clinical situation.

show abstract

“…The EMA and FDA have approved several drugs in this class of medication for the treatment of T2D including dapagliflozin, empagliflozin, canagliflozin and ertugliflozin. However, none are yet approved by the EMA or FDA specifically for the treatment of obesity, though trials in obese people without T2D have shown promising results [61].…”

Section: Sodium-glucose Co-transporter-2 Inhibitorsmentioning

confidence: 99%

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

2020

View full text Add to dashboard Cite

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.

show abstract

Emerging Role of SGLT-2 Inhibitors for the Treatment of Obesity

Cited by 177 publications

References 100 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

Type 2 Diabetes Remission and Substantial Body Weight Reduction Achieved with Metformin and a Sodium-Glucose Cotransporter 2 Inhibitor

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

Contact Info

Product

Resources

About