Skip to main content
Top

09-30-2016 | SGLT2 inhibitors | Article

Combination therapy with GLP-1 analogues and SGLT-2 inhibitors in the management of diabesity: the real world experience

Journal: Endocrine

Authors: Herpreet Deol, Leoni Lekkakou, Ananth K. Viswanath, Joseph M. Pappachan

Publisher: Springer US

Abstract

Diabesity—obesity resulting in diabetes—is a major health problem globally because of the obesity epidemic. Several anti-diabetic medications cause weight gain and may worsen obesity, and possibly diabeisty. Two recent small retrospective cohort studies showed weight loss and diabetes improvement with combination of glucagon-like peptide-1 (GLP-1) agonists and sodium-glucose co-transporter type-2 (SGLT-2) inhibitors in obese subjects. We assessed the effect of combination therapy with GLP-1 agonists and SGLT-2 inhibitors in the management of diabesity in a retrospective study at the Wolverhampton Diabetes Centre. Out of 79 patients on this combination regimen with other anti-diabetic medications, 37 cases who had follow up at 3–6 months were studied. Mean age and duration of follow up were 57.4 (+/−7.8) and 139 (+/−32.6) days, respectively. Twenty-two patients (59.5 %) were Asians. Statistically significant improvements in clinical parameters such as body weight reduction (3.07 kg), glycated haemoglobin (HbA1c) reduction (1.05 %), lower BMI (−1.13 kg/M2) and insulin dose reduction (6.8 units) were observed (p < 0.05 for all) in patients on combination regimen. Linear regression analysis showed that baseline HbA1c and baseline insulin dose were independent predictors of HbA1c reduction and insulin dose reduction, respectively. Our results suggest that combination therapy with GLP-1 agonists and SGLT-2 inhibitors is a promising option for patients with diabesity.
Literature
1.
World Health Organization. Obesity and overweight. Geneva, Switzerland: World Health Organization, 2015. http://​www.​who.​int/​mediacentre/​factsheets/​fs311/​en/​. Accessed 30 March 2016
2.
E.A. Sims, E. Danforth Jr, E.S. Horton, G.A. Bray, J.A. Glennon, L.B. Salans, Endocrine and metabolic effects of experimental obesity in man. Recent Prog. Horm. Res. 29, 457–496 (1973)PubMed
3.
P.R. Schauer, D.L. Bhatt, J.P. Kirwan, K. Wolski, S.A. Brethauer, S.D. Navaneethan, A. Aminian, C.E. Pothier, E.S. Kim, S.E. Nissen, S.R. Kashyap, STAMPEDE Investigators. Bariatric surgery versus intensive medical therapy for diabetes—3-year outcomes. N. Engl. J. Med. 370, 2002–2013 (2014)CrossRefPubMed
4.
G. Mingrone, S. Panunzi, A. De Gaetano, C. Guidone, A. Iaconelli, G. Nanni et al., Bariatric-metabolic surgery versus conventional medical treatment in obese patients with type 2 diabetes: 5 year follow-up of an open-label, single-centre, randomised controlled trial. Lancet 386(9997), 964–973 (2015)CrossRefPubMed
5.
G.F. Paulus, L.E. de Vaan, F.J. Verdam, N.D. Bouvy, T.A. Ambergen, L.W. van Heurn, Bariatric surgery in morbidly obese adolescents: a systematic review and meta-analysis. Obes. Surg. 25, 860–878 (2015)CrossRefPubMedPubMedCentral
6.
R.M. Saroka, M.P. Kane, R.S. Busch, J. Watsky, R.A. Hamilton, SGLT-2 inhibitor therapy added to GLP-1 agonist therapy in the management of T2DM. Endocr. Pract. 21, 1315–1322 (2015)CrossRefPubMed
7.
K. Kaku, H. Maegawa, Y. Tanizawa, A. Kiyosue, Y. Ide, T. Tokudome, Y. Hoshino, J. Yang, A.M. Langkilde, Dapagliflozin as monotherapy or combination therapy in Japanese patients with type 2 diabetes: an open-label study. Diabetes Ther 5, 415–433 (2014)CrossRefPubMedPubMedCentral
8.
L. Curtis, M.A. Humayun, J. Walker, K. Hampton, H. Partridge, Addition of SGLT2 inhibitor to GLP-1 agonist therapy in people with type 2 diabetes and suboptimal glycaemic control. Practical Diabetes 33, 129–132 (2016)CrossRef
9.
K. Esposito, P. Chiodini, A. Capuano, M.I. Maiorino, G. Bellastella, D. Giugliano, Baseline glycemic parameters predict the hemoglobin A1c response to DPP-4 inhibitors : meta-regression analysis of 78 randomized controlled trials with 20,053 patients. Endocrine 46, 43–51 (2014)CrossRefPubMed
10.
R.R. Henry, J.B. Buse, G. Sesti, M.J. Davies, K.H. Jensen, J. Brett, R.E. Pratley, Efficacy of antihyperglycemic therapies and the influence of baseline hemoglobinA(1c): a meta-analysis of the liraglutide development program. Endocr. Pract. 17, 906–913 (2011)CrossRefPubMed
11.
J. Rosenstock, L. Hansen, P. Zee, Y. Li, W. Cook, B. Hirshberg, N. Iqbal, Dual add-on therapy in type 2 diabetes poorly controlled with metformin monotherapy: a randomized double-blind trial of saxagliptin plus dapagliflozin addition versus single addition of saxagliptin or dapagliflozin to metformin. Diabetes Care 38, 376–383 (2015)CrossRefPubMed
12.
R. Huxley, W.P. James, F. Barzi, J.V. Patel, S.A. Lear, P. Suriyawongpaisal, E. Janus, I. Caterson, P. Zimmet, D. Prabhakaran, S. Reddy, M. Woodward, Obesity in Asia Collaboration. Ethnic comparisons of the cross-sectional relationships between measures of body size with diabetes and hypertension. Obes. Rev. 9(Suppl 1), 53–61 (2008)CrossRefPubMed
13.
S. Haldar, S.C. Chia, C.J. Henry, Body composition in Asians and Caucasians: comparative analyses and influences on cardiometabolic outcomes. Adv. Food Nutr. Res. 75, 97–154 (2015)CrossRefPubMed
14.
D.S. Shyangdan, O.A. Uthman, N. Waugh, SGLT-2 receptor inhibitors for treating patients with type 2 diabetes mellitus: a systematic review and network meta-analysis. BMJ Open 6, e009417 (2016)CrossRefPubMedPubMedCentral
15.
N.M. Maruthur, E. Tseng, S. Hutfless, L.M. Wilson, C. Suarez-Cuervo, Z. Berger, Y. Chu, E. Iyoha, J.B. Segal, S. Bolen, Diabetes medications as monotherapy or metformin-based combination therapy for type 2 diabetes: a systematic review and meta-analysis. Ann. Intern. Med. 164, 740–751 (2016)CrossRefPubMed
16.
B. Zinman, C. Wanner, J.M. Lachin, D. Fitchett, E. Bluhmki, S. Hantel et al., Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N. Engl. J. Med. 373, 2117–2128 (2015)CrossRefPubMed
17.
C. Wanner, S.E. Inzucchi, J.M. Lachin, D. Fitchett, M. von Eynatten, M. Mattheus et al., Empagliflozin and progression of kidney disease in type 2 diabetes. N. Engl. J. Med. 375, 323–334 (2016)CrossRefPubMed
18.
S.P. Marso, G.H. Daniels, K. Brown-Frandsen, P. Kristensen, J.F. Mann, M.A. Nauck et al., Liraglutide and cardiovascular outcomes in type 2 diabetes. N. Engl. J. Med. 375, 311–322 (2016)CrossRefPubMed
19.
M. May, C. Schindler, Clinically and pharmacologically relevant interactions of antidiabetic drugs. Ther. Adv. Endocrinol. Metab. 7, 69–83 (2016)CrossRefPubMedPubMedCentral
20.
S.I. Taylor, J.E. Blau, K.I. Rother, SGLT2 inhibitors may predispose to ketoacidosis. J. Clin. Endocrinol. Metab. 100, 2849–2852 (2015)CrossRefPubMedPubMedCentral
21.
M.M. Smits, L. Tonneijck, M.H. Muskiet, M.H. Kramer, D.L. Cahen, D.H. van Raalte, Gastrointestinal actions of glucagon-like peptide-1-based therapies: glycaemic control beyond the pancreas. Diabetes Obes. Metab. 18, 224–235 (2016)CrossRefPubMed
22.
F. Sun, S. Wu, S. Guo, K. Yu, Z. Yang, L. Li, Y. Zhang, L. Ji, S. Zhan, Effect of GLP-1 receptor agonists on waist circumference among type 2 diabetes patients: a systematic review and network meta-analysis. Endocrine 48, 794–803 (2015)CrossRefPubMed
23.
R.P.Monica Reddy, S.E. Inzucchi, SGLT2 inhibitors in the management of type 2 diabetes. Endocrine 53, 364–372 (2016)CrossRef
24.
Y.G. Kim, S. Hahn, T.J. Oh, K.S. Park, Y.M. Cho, Differences in the HbA1c-lowering efficacy of glucagon-like peptide-1 analogues between Asians and non-Asians: a systematic review and meta-analysis. Diabetes Obes. Metab. 16, 900–909 (2014)CrossRefPubMed
25.
S.E. Inzucchi, R.M. Bergenstal, J.B. Buse, M. Diamant, E. Ferrannini, M. Nauck et al., Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 38, 140–149 (2015)CrossRefPubMed

Be confident that your patient care is up to date

Medicine Matters is being incorporated into Springer Medicine, our new medical education platform. 

Alongside the news coverage and expert commentary you have come to expect from Medicine Matters diabetes, Springer Medicine's complimentary membership also provides access to articles from renowned journals and a broad range of Continuing Medical Education programs. Create your free account »