With the increasing prevalence of obesity and associated co-morbidities, including impaired glucose tolerance and type 2 diabetes mellitus, novel treatment strategies are needed. |
SGLT2 inhibitor monotherapy does not provide sufficient weight loss for successful treatment of obesity. |
Co-administration of SGLT2 inhibitors together with agents that reduce food intake target complementary mechanisms and represent an effective weight loss therapy. |
1 Introduction
2 Clinical Effect of SGLT2 Inhibitors
3 Glycemic Control
Reference, year | Duration (week) |
N
| Treatment arms | Bodyweight change from baseline (kg) | Other effects |
---|---|---|---|---|---|
SGLT2 inhibitors | |||||
Bays et al. 2014 [29] | 12 | 376 | Placebo Canagliflozin 50 mg Canagliflozin 100 mg Canagliflozin 300 mg | − 1.1 − 1.9 − 2.8 − 2.4 | ↓ BMI, SBP ↑ UGE/creatinine ratio, LDL-C/HDL-C, IWQOL-Lite total scores = TG, HDL-C, FPG, HbA1c, pulse rate |
Napolitano et al. 2014 [82] | 8 | 30 | Placebo + diet (− 500 cal) Remogliflozin etaborate 250 mg + diet (− 500 cal) Sergliflozin etaborate 1,000 mg + diet (− 500 cal) | − 5.1 − 7.6 − 6.1 | ↓ Fat mass, fat free mass, leptin/adiponectin ↑ UGE |
Ramirez-Rodriguez et al. 2018 [23] | 12 | 24 | Placebo Dapagliflozin 10 mg | − 1.0 − 3.0 | ↓ FPG, uric acid |
SGLT2 inhibitors +GLP1-RA | |||||
Lundkvist et al. 2016 [83] | 24 | 50 | Placebo Dapagliflozin 10 mg + Exenatide 2 mg | − 0.4 − 4.5 | ↓ VAT, SAT, TAT, HbA1c, 2-h PG, IFG, SBP ↑ UGE = total lean tissue, liver fat, serum lipids |
Lundkvist et al. 2017 [21] | 52 | 50 | Dapagliflozin 10 mg + Exenatide 2 mg | − 5.7 | |
SGLT2 inhibitors + phentermine | |||||
Hollander et al. 2017 [42] | 26 | 335 | Placebo Canagliflozin 300 mg Phentermine 15 mg Canagliflozin + Phentermine 15 mg | − 0.6 − 1.9 − 4.1 − 7.3 | ↓ SBP ↑ Pulse rate (Phentermine, Canagliflozin + Phentermine) = plasma lipids |
4 Effects on Body Weight and Adiposity
Reference | Duration to end point (week) |
N
| Study population | Treatment arms | Bodyweight change from baseline (kg) |
---|---|---|---|---|---|
SGLT2 inhibitor | |||||
Bailey et al. 2012 [84] | 24 | 282 | T2D | Placebo Dapagliflozin 1 mg Dapagliflozin 2.5 mg Dapagliflozin 5 mg | − 1.0 − 2.7a − 2.6a − 2.7a |
Ferrannini et al. 2010 [85] | 24 | 485 | T2D | Placebo Dapagliflozin 2.5 mg Dapagliflozin 5 mg Dapagliflozin 10 mg | − 2.2 − 3.3 − 2.8 − 3.2 |
Ji et al. 2014 [86] | 24 | 326 | T2D | Placebo Dapagliflozin 5 mg Dapagliflozin 10 mg | − 0.3 − 1.6a − 2.6a |
Kaku et al. 2014 [87] | 24 | 261 | T2D | Placebo Dapagliflozin 5 mg Dapagliflozin 10 mg | − 0.8 − 2.1a − 2.2a |
Lambers Heerspink et al. 2013 [58] | 12 | 75 | T2D | Placebo Dapagliflozin 10 mg | − 0.1 − 2.4a |
SGLT2 inhibitor + metformin or sulfonylurea | |||||
Bailey et al. 2010 [88] | 24 | 546 | T2D | Placebo + Metformin Dapagliflozin 2.5 mg Dapagliflozin 5 mg Dapagliflozin 10 mg | − 0.9 − 2.2a − 3.0a − 2.9a |
Bailey et al. 2013 [89] | 102 | 546 | T2D | Placebo + Metformin Dapagliflozin 2.5 mg Dapagliflozin 5 mg Dapagliflozin 10 mg | + 1.4 − 1.1a − 1.7a − 1.7a |
Bolinder et al. 2012 [90] | 24 | 182 | T2D | Placebo + Metformin Dapagliflozin 10 mg | − 0.9 − 3.0a |
Bolinder et al. 2014 [37] | 102 | 182 | T2D | Placebo + Metformin Dapagliflozin 10 mg | − 2.1 − 4.5a |
Strojek et al. 2011 [91] | 24 | 597 | T2D | Placebo + Glimepiride Dapagliflozin 2.5 mg + Glimepiride Dapagliflozin 5 mg + Glimepiride Dapagliflozin 10 mg + Glimepiride | − 0.7 − 1.2 − 1.6a − 2.3a |
Strojek et al. 2015 [92] | 48 | 597 | T2D | Placebo + Glimepiride Dapagliflozin 2.5 mg + Glimepiride Dapagliflozin 5 mg + Glimepiride Dapagliflozin 10 mg + Glimepiride | − 0.8 − 1.4 − 1.5a − 2.4a |
Bailey et al. 2015 [38] | 102 | 274 | T2D | Placebo + Metformin Dapagliflozin 2.5 mg Dapagliflozin 5 mg Dapagliflozin 10 mg | − 1.3 − 0.6 − 1.6 − 3.9a |
Nauck et al. 2011 [93] | 52 | 814 | T2D | Glipizide + Metformin Dapagliflozin + Met | + 1.4 − 3.2a |
Nauck et al. 2014 [94] | 104 | 814 | T2D | Glip + Metformin Dapagliflozin + Metformin | + 1.4 − 3.7a |
Del Prato et al. 2015 [39] | 208 | 814 | T2D | Glipizide + Metformin Dapagliflozin (up to 20 mg) + Metformin | + 0.7 − 4.4a |
SGLT2 inhibitors + GLP1-RA | |||||
Fulcher et al. 2016 [95] | 18 | 95 | T2D | Placebo + GLP1-RA 300 mg Canagliflozin 100 mg + GLP1-RA 300 mg Canagliflozin 300 mg + GLP1-RA 300 mg | − 0.6 − 3.3a − 3.9a |
Frias et al. 2016 [17] | 28 | 695 | T2D | Dapagliflozin 10 mg Exenatide 2 mg Dapagliflozin 10 mg + Exenatide 2 mg | − 2.2 − 1.6 − 3.6a |
Ludvik et al. 2018 [96] | 24 | 424 | T2D | SGLT2 inhibitor + Placebo SGLT2 inhibitor + Dulaglutide 0.75 mg SGLT2 inhibitor + Dulaglutide 1.5 mg | − 2.1 − 2.6 − 3.1a |
SGLT2 inhibitor ± DPP-4 inhibitor ± metformin | |||||
Jabbour et al. 2014 [97] | 24 | 432 | T2D | Sitagliptin 100 mg + Placebo Sitagliptin 100 mg + Dapagliflozin 10 mg | − 0.1 − 1.9 |
Fulcher et al. 2016 [95] | 18 | 316 | T2D | DPP-4 inhibitor + Placebo DPP-4 inhibitor + Canagliflozin 100 mg DPP-4 inhibitor + Canagliflozin 300 mg | − 0.8 − 2.7a − 3.5a |
DeFronzo et al. 2015 [98] | 52 | 674 | T2D | Linagliptin 5 mg Empagliflozin 25 mg + Linagliptin 5 mg Empagliflozin 10 mg + Linagliptin 5 mg Empagliflozin 25 mg Empagliflozin 10 mg | − 0.3 − 3.1a − 2.7 − 2.8 − 2.9 |
Pratley et al. 2018 [99] | 52 | 1232 | T2D | Sitagliptin 100 mg Ertugliflozin 5 mg Ertugliflozin 15 mg Sitagliptin 100 mg + Ertugliflozin 5 mg Sitagliptin 100 mg + Ertugliflozin 15 mg | − 0.1 − 2.4 − 3.2 − 2.4 − 2.8 |
Rosenstock et al. 2018 [100] | 24 | 534 | T2D | Saxagliptin 5 mg + Placebo Dapagliflozin10 mg + Placebo Saxagliptin 5 mg + Dapagliflozin 10 mg | 0.0 − 2.4 − 2.1 |
Mathieu et al. 2016 [101] | 52 | 294 | T2D | Saxagliptin 5 mg + Placebo Saxagliptin 5 mg + Dapagliflozin 10 mg | − 0.4 − 2.1 |
SGLT2 inhibitor + thiazolidinediones | |||||
Rosenstock et al. 2012 [102] | 48 | 420 | T2D | Pioglitazone Pioglitazone + Dapagliflozin 5 mg Pioglitazone + Dapagliflozin 10 mg | + 3.0 + 1.4 + 0.7 |
Kovacs et al. 2014 [103] | 24 | 498 | T2D | Pioglitazone Pioglitazone + Empagliflozin 10 mg Pioglitazone + Empagliflozin 25 mg | + 0.3 − 1.6a − 1.5a |
SGLT2 inhibitor + insulin | |||||
Wilding et al. 2014 [104] | 104 | 808 | T2D | Insulin Insulin + Dapagliflozin 2.5 mg Insulin + Dapagliflozin 5 mg Insulin + Dapagliflozin 10 mg | + 1.8 − 1.0a − 1.0a − 1.5a |
Rosenstock et al. 2014 [105] | 52 | 563 | T2D | Insulin + Placebo Insulin + Empagliflozin 10 mg Insulin + Empagliflozin 25 mg Insulin + Dapagliflozin 10 mg | + 0.4 − 2.0a − 2.0a |