Download PDF
Drug Res (Stuttg) 2021; 71(09): 477-488
DOI: 10.1055/a-1555-2797
Review

Effects of Sitagliptin as Monotherapy and Add-On to Metformin on Weight Loss among Overweight and Obese Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis

Leila Janani
1   Department of Biostatistics, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
,
Hadi Bamehr
2   Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
,
Kiarash Tanha
1   Department of Biostatistics, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
,
Parastoo Mirzabeigi
3   Department of Clinical Pharmacy, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran
,
Hamed Montazeri
4   Department of Pharmacognosy and Pharmaceutical Biotechnology, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran
,
Parastoo Tarighi
5   Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
› Author Affiliations
› Further Information
Also available at
   Permissions and Reprints

Abstract

Background Sitagliptin is known as an antidiabetic agent inhibiting the dipeptidyl peptidase-4. Although sitagliptin may influence weight, controversial results have been reported, and there is no general agreement on this issue. Therefore, this study assessed the effect of sitagliptin as monotherapy and add-on therapy to metformin on weight reduction in overweight or obese cases with type 2 diabetes.

Methods We reviewed the following databases to identify all relevant papers published until 1st April 2021: Web of Science, MEDLINE, Embase, Scopus, Cochrane Central Register of Controlled Trials Cochrane Library, and Google Scholar. The research included all clinical trials investigating the effect of sitagliptin in obese or overweight adult patients with type 2 diabetes without any language restriction.

Results In total, eighteen randomized controlled trials with 2009 participants were included in our meta-analysis. Results showed supplementation of sitagliptin has led to weight loss for sitagliptin treated (MD  −0.99; 95% CI; (−1.87, −0.12); p=0.026)) and sitagliptin+metformin treated groups (MD  −1.09; 95% CI; (−1.69, −0.49); p<0.001)). Also, the intervention has influenced body mass index in sitagliptin treated (MD  −0.23; 95% CI; (−0.45, 0.02); p=0.033)) and sitagliptin+metformin treated groups (MD −0.52; 95% CI; (−0.96, 0.08); p=0.020)) comparing to placebo.

Conclusion Our results demonstrated that sitagliptin administration with or without metformin might reduce the body weight and body mass index if these drugs are taken for more than 6 months.

Key words

Systematic review - Meta-analysis - Randomised clinical trial - Type 2 diabetes - Sitagliptin - Overweight - Metformin


Publication History

Received: 19 February 2021

Accepted: 18 July 2021

Article published online:
13 August 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Nguyen T, Lau DC. The obesity epidemic and its impact on hypertension. Canadian Journal of Cardiology 2012; 28 (3): 326-333
    CrossrefPubMedGoogle Scholar
  • 2 Popa AR, Fratila O, Rus M. et al Risk factors for adiposity in the urban population and influence on the prevalence of overweight and obesity. Experimental and Therapeutic Medicine 2020; 20: 129-133
    PubMedGoogle Scholar
  • 3 Grundy SM. Multifactorial causation of obesity: implications for prevention. The American Journal of Clinical Nutrition 1998; 67: 563S-572SS
    CrossrefPubMedGoogle Scholar
  • 4 Wang YC, McPherson K, Marsh T. et al Health and economic burden of the projected obesity trends in the USA and the UK. The Lancet 2011; 378: 815-825
    CrossrefPubMedGoogle Scholar
  • 5 Guo X, Zhang T, Shi L. et al The relationship between lipid phytochemicals, obesity and its related chronic diseases. Food & Function 2018; 9: 6048-6062
    CrossrefPubMedGoogle Scholar
  • 6 Anderson JW, Kendall CW, Jenkins DJ. Importance of weight management in type 2 diabetes: review with meta-analysis of clinical studies. Journal of the American college of nutrition 2003; 22: 331-339
    CrossrefPubMedGoogle Scholar
  • 7 Wing RR, Lang W, Wadden TA. et al Benefits of modest weight loss in improving cardiovascular risk factors in overweight and obese individuals with type 2 diabetes. Diabetes care 2011; 34: 1481-1486
    CrossrefPubMedGoogle Scholar
  • 8 O’Keefe Jr JH, Miles JM, Harris WH. et al editors. Improving the adverse cardiovascular prognosis of type 2 diabetes. Mayo Clinic Proceedings. 1999. 74(2). 171-180
    CrossrefGoogle Scholar
  • 9 Duckworth WC, McCarren M, Abraira C. Glucose control and cardiovascular complications: the VA Diabetes Trial. Diabetes Care 2001; 24: 942-945
    CrossrefPubMedGoogle Scholar
  • 10 Amatruda JM, Richeson JF, Welle SL. et al The safety and efficacy of a controlled low-energy (‘very-low-calorie’) diet in the treatment of non-insulin-dependent diabetes and obesity. Archives of Internal Medicine 1988; 148: 873-877
    CrossrefPubMedGoogle Scholar
  • 11 Stern MP, Patterson JK, Haffner SM. et al Lack of awareness and treatment of hyperlipidemia in type II diabetes in a community survey. JAMA 1989; 262: 360-364
    CrossrefPubMedGoogle Scholar
  • 12 Velazquez A, Apovian CM. Updates on obesity pharmacotherapy. Annals of the New York Academy of Sciences 2018; 1411: 106-119
    CrossrefPubMedGoogle Scholar
  • 13 Association AD. Standards of Medical Care in Diabetes—2021 Abridged for Primary Care Providers. Clinical Diabetes 2021; 39: 14-43
    CrossrefPubMedGoogle Scholar
  • 14 Phung OJ, Scholle JM, Talwar M. et al Effect of noninsulin antidiabetic drugs added to metformin therapy on glycemic control, weight gain, and hypoglycemia in type 2 diabetes. Jama 2010; 303: 1410-1418
    CrossrefPubMedGoogle Scholar
  • 15 Robinson LE, Holt TA, Rees K. et al Effects of exenatide and liraglutide on heart rate, blood pressure and body weight: systematic review and meta-analysis. BMJ open 2013; 3(1) e001986
    CrossrefPubMedGoogle Scholar
  • 16 Derosa G, Maffioli P. Dipeptidyl peptidase-4 inhibitors: 3 years of experience. Diabetes technology & therapeutics 2012; 14: 350-364
    CrossrefPubMedGoogle Scholar
  • 17 Butryn ML, Webb V, Wadden TA. Behavioral treatment of obesity. Psychiatric Clinics 2011; 34: 841-859
    PubMedGoogle Scholar
  • 18 Drucker D, Easley C. Kirkpatrick P. Sitagliptin. Nature Reviews Drug Discovery 2007; 6: 109
    CrossrefPubMedGoogle Scholar
  • 19 Holst JJ. The physiology of glucagon-like peptide 1. Physiological reviews 2007; 87: 1409-1439
    CrossrefPubMedGoogle Scholar
  • 20 Holst JJ, Vilsbøll T, Deacon CF. The incretin system and its role in type 2 diabetes mellitus. Molecular and cellular endocrinology 2009; 297: 127-136
    CrossrefPubMedGoogle Scholar
  • 21 Drucker DJ. The biology of incretin hormones. Cell Metabolism 2006; 3: 153-165
    CrossrefPubMedGoogle Scholar
  • 22 Schirra J, Göke B. The physiological role of GLP-1 in human: incretin, ileal brake or more?. Regulatory Peptides 2005; 128: 109-115
    CrossrefPubMedGoogle Scholar
  • 23 Aulinger BA, Bedorf A, Kutscherauer G. et al Defining the role of GLP-1 in the enteroinsulinar axis in type 2 diabetes using DPP-4 inhibition and GLP-1 receptor blockade. Diabetes 2014; 63: 1079-1092
    CrossrefPubMedGoogle Scholar
  • 24 Scott LJ. Sitagliptin: a review in type 2 diabetes. Drugs. 2017; 77: 209-224
    CrossrefPubMedGoogle Scholar
  • 25 Ferreira L, Teixeira-de-Lemos E, Pinto F. et al Effects of sitagliptin treatment on dysmetabolism, inflammation, and oxidative stress in an animal model of type 2 diabetes (ZDF rat). Mediators of inflammation 2010; 2010
    PubMedGoogle Scholar
  • 26 Tran S, Retnakaran R, Zinman B. et al Efficacy of glucagon-like peptide-1 receptor agonists compared to dipeptidyl peptidase-4 inhibitors for the management of type 2 diabetes: A meta-analysis of randomized clinical trials. Diabetes, Obesity and Metabolism 2018; 20: 68-76
    CrossrefPubMedGoogle Scholar
  • 27 Ling J, Cheng P, Ge L. et al The efficacy and safety of dipeptidyl peptidase-4 inhibitors for type 2 diabetes: a Bayesian network meta-analysis of 58 randomized controlled trials. Acta Diabetologica 2019; 56: 249-272
    CrossrefPubMedGoogle Scholar
  • 28 Garg SK, Moser EG, Bode BW. et al Effect of sitagliptin on post-prandial glucagon and GLP-1 levels in patients with type 1 diabetes: investigator-initiated, double-blind, randomized, placebo-controlled trial. Endocrine Practice 2013; 19: 19-28
    CrossrefPubMedGoogle Scholar
  • 29 Gül ÖÖ, Kıyıcı S, Ersoy C. et al Effect of sitagliptin monotherapy on serum total ghrelin levels in people with type 2 diabetes. Diabetes research and clinical Practice 2011; 94: 212-216
    CrossrefPubMedGoogle Scholar
  • 30 Lavalle-González F, Januszewicz A, Davidson J. et al Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy: a randomised trial. Diabetologia. 2013; 56: 2582-2592
    CrossrefPubMedGoogle Scholar
  • 31 Ristic S, Byiers S, Foley J. et al Improved glycaemic control with dipeptidyl peptidase-4 inhibition in patients with type 2 diabetes: vildagliptin (LAF237) dose response. Diabetes. Obesity and Metabolism 2005; 7: 692-698
    CrossrefPubMedGoogle Scholar
  • 32 Pi-Sunyer FX, Schweizer A, Mills D. et al Efficacy and tolerability of vildagliptin monotherapy in drug-naive patients with type 2 diabetes. Diabetes Research and Clinical Practice 2007; 76: 132-138
    CrossrefPubMedGoogle Scholar
  • 33 Higgins J, Altman DG. Assessing risk of bias in included studies Cochrane Handbook for Systematic Reviews of Interventions: Cochrane Book Series . 2008
    Google Scholar
  • 34 Borenstein M, Higgins J, Hedges LV. et al Basics of meta-analysis: I 2 is not an absolute measure of heterogeneity in a meta-analysis. Res Synth Methods. 2017;8(1):5–18.
    Google Scholar
  • 35 Fuchigami A, Shigiyama F, Kitazawa T. et al Efficacy of dapagliflozin versus sitagliptin on cardiometabolic risk factors in Japanese patients with type 2 diabetes: a prospective, randomized study (DIVERSITY-CVR). Cardiovascular diabetology 2020; 19: 1-11
    CrossrefPubMedGoogle Scholar
  • 36 Webb DR, Htike ZZ, Swarbrick DJ. et al A randomized, open-label, active comparator trial assessing the effects of 26 weeks of liraglutide or sitagliptin on cardiovascular function in young obese adults with type 2 diabetes. Diabetes, Obesity and Metabolism 2020; 22: 1187-1196
    CrossrefPubMedGoogle Scholar
  • 37 Derosa G, Carbone A, Franzetti I. et al Effects of a combination of sitagliptin plus metformin vs metformin monotherapy on glycemic control, β-cell function and insulin resistance in type 2 diabetic patients. Diabetes Research and Clinical Practice 2012; 98: 51-60
    CrossrefPubMedGoogle Scholar
  • 38 Ferjan S, Janez A, Jensterle M. Dipeptidyl peptidase-4 inhibitor sitagliptin prevented weight regain in obese women with polycystic ovary syndrome previously treated with liraglutide: a pilot randomized study. Metabolic syndrome and related disorders 2017; 15: 515-520
    CrossrefPubMedGoogle Scholar
  • 39 Smits MM, Fluitman KS, Herrema H. et al Liraglutide and sitagliptin have no effect on intestinal microbiota composition: A 12-week randomized placebo-controlled trial in adults with type 2 diabetes. Diabetes & Metabolism 2021; 101223
    CrossrefPubMedGoogle Scholar
  • 40 Yan J, Yao B, Kuang H. et al Liraglutide, sitagliptin, and insulin glargine added to metformin: the effect on body weight and intrahepatic lipid in patients with type 2 diabetes mellitus and nonalcoholic fatty liver disease. Hepatology. 2019; 69: 2414-2426
    CrossrefPubMedGoogle Scholar
  • 41 Kitazawa M, Katagiri T, Suzuki H. et al A 52–week randomized controlled trial of ipragliflozin or sitagliptin in type 2 diabetes combined with metformin: The N-ISM study. Diabetes, Obesity and Metabolism 2021; 23: 811-821
    CrossrefPubMedGoogle Scholar
  • 42 Ji L, Dong X, Li Y. et al Efficacy and safety of once-weekly semaglutide vs once-daily sitagliptin as add-on to metformin in patients with type 2 diabetes (SUSTAIN China): a 30–week double-blind, phase 3a, randomised trial. Diabetes, Obesity and Metabolism 2021; 23: 404-414
    CrossrefPubMedGoogle Scholar
  • 43 Bhosle DS, Bhagat AH, Patil AD. et al Effects of a fixed-dose combination of sitagliptin and metformin versus respective monotherapies in newly diagnosed type 2 diabetic subjects. International Journal of Diabetes in Developing Countries 2017; 37: 16-20
    CrossrefPubMedGoogle Scholar
  • 44 Hussain M, Rafique MA, Iqbal J. et al Effect of sitagliptin and glimepiride on C-reactive protein (CRP) in overweight Type-2 diabetic patients. Pakistan Journal of Medical Sciences 2019; 35: 383
    CrossrefPubMedGoogle Scholar
  • 45 Ajmani AK, Agrawal A, Prasad B. et al Efficacy and safety of evogliptin versus sitagliptin as an add-on therapy in Indian patients with type 2 diabetes mellitus inadequately controlled with metformin: A 24-week randomized, double-blind, non-inferiority, EVOLUTION INDIA study. Diabetes Research and Clinical practice 2019; 157: 107860
    CrossrefPubMedGoogle Scholar
  • 46 Halvorsen YD, Lock JP, Zhou W. et al A 24–week, randomized, double-blind, active-controlled clinical trial comparing bexagliflozin with sitagliptin as an adjunct to metformin for the treatment of type 2 diabetes in adults. Diabetes, Obesity and Metabolism 2019; 21: 2248-2256
    CrossrefPubMedGoogle Scholar
  • 47 Hiruma S, Shigiyama F, Hisatake S. et al A prospective randomized study comparing effects of empagliflozin to sitagliptin on cardiac fat accumulation, cardiac function, and cardiac metabolism in patients with early-stage type 2 diabetes: the ASSET study. Cardiovascular Diabetology 2021; 20: 1-13
    CrossrefPubMedGoogle Scholar
  • 48 Gadde KM, Vetter ML, Iqbal N. et al Efficacy and safety of autoinjected exenatide once-weekly suspension versus sitagliptin or placebo with metformin in patients with type 2 diabetes: T he DURATION-NEO-2 randomized clinical study. Diabetes, Obesity and Metabolism 2017; 19: 979-988
    CrossrefPubMedGoogle Scholar
  • 49 Aaboe K, Knop F, Vilsbøll T. et al Twelve weeks treatment with the DPP-4 inhibitor, sitagliptin, prevents degradation of peptide YY and improves glucose and non-glucose induced insulin secretion in patients with type 2 diabetes mellitus. Diabetes, Obesity and Metabolism 2010; 12: 323-333
    CrossrefPubMedGoogle Scholar
  • 50 Rosenstock J, Allison D, Birkenfeld AL. et al Effect of additional oral semaglutide vs sitagliptin on glycated hemoglobin in adults with type 2 diabetes uncontrolled with metformin alone or with sulfonylurea: the PIONEER 3 randomized clinical trial. Jama. 2019; 321: 1466-1480
    CrossrefPubMedGoogle Scholar
  • 51 Strasser B, Schobersberger W. Evidence for resistance training as a treatment therapy in obesity. Journal of Obesity 2011; 2011
    PubMedGoogle Scholar
  • 52 Sallam RM, Alayoubi SMZ, Al-Daghri NM. et al Gender-Specific profiles of cardiovascular disease in type 2 diabetes mellitus: A cross-sectional study. Journal of Nature and Science of Medicine 2018; 1: 74
    PubMedGoogle Scholar
  • 53 Kopelman P. Health risks associated with overweight and obesity. Obesity reviews 2007; 8: 13-17
    CrossrefPubMedGoogle Scholar
  • 54 Fernandes JC, Collaborators GO. Health effects of overweight and obesity in 195 countries over 25 years. New England Journal of Medicine 2017; 377: 13-27
    CrossrefPubMedGoogle Scholar
  • 55 Shin SJ. Glucagon-like peptide-1 receptor agonists and their effects on weight reduction. Journal of Diabetes Investigation 2012; 3: 490
    CrossrefPubMedGoogle Scholar
  • 56 Pareek M, Schauer PR, Kaplan LM. et al Metabolic surgery: weight loss, diabetes, and beyond. Journal of the American College of Cardiology 2018; 71: 670-687
    CrossrefPubMedGoogle Scholar
  • 57 Nauck M, Meininger G, Sheng Do. et al Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, compared with the sulfonylurea, glipizide, in patients with type 2 diabetes inadequately controlled on metformin alone: a randomized, double-blind, non-inferiority trial. Diabetes, Obesity and Metabolism 2007; 9: 194-205
    CrossrefPubMedGoogle Scholar
  • 58 Dicker D. DPP-4 inhibitors: impact on glycemic control and cardiovascular risk factors. Diabetes care 2011; 34: S276-S278
    CrossrefPubMedGoogle Scholar
  • 59 Lovshin JA, Drucker DJ. Incretin-based therapies for type 2 diabetes mellitus. Nature Reviews Endocrinology 2009; 5: 262
    CrossrefPubMedGoogle Scholar
  • 60 Amori RE, Lau J, Pittas AG. Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis. Jama. 2007; 298: 194-206
    CrossrefPubMedGoogle Scholar
  • 61 Sethi MK, Singh D, Murti K. et al DPP-4 inhibitors: A novel approach for management of type-2 diabetes mellitus World Journal of Pharmaceutical Sciences. 2014 2(10).
    Google Scholar