Skip to main content

12-01-2017 | SGLT2 inhibitors | Article

Effectiveness of long-term treatment with SGLT2 inhibitors: real-world evidence from a specialized diabetes center

Journal: Diabetology & Metabolic Syndrome

Authors: Yotsapon Thewjitcharoen, Nalin Yenseung, Areeya Malidaeng, Soontaree Nakasatien, Phawinpon Chotwanvirat, Sirinate Krittiyawong, Ekgaluck Wanothayaroj, Thep Himathongkam

Publisher: BioMed Central



Diabetes is a progressive disease needing multiple drugs for achieving and maintaining good glycemic control. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) is a novel class of anti-diabetic agent which offers several beneficial effects. However, the long-term effectiveness in clinical practice and safety data of SGLT2 inhibitors is limited, especially in Asian patients. To better understand the effectiveness of SGLT2i in clinical practice, we conducted a retrospective evaluation of patients with diabetes on SGLT2i.


This retrospective observational study uses data of patients with diabetes who had been prescribed SGLT2i and continued to use at least 6 months at Theptarin Hospital, Bangkok. The characteristics of patients, changes in glycemic control and body weight at 3, 6, 12, 18, 24 months and the last follow-up were evaluated.


A total of 189 patients with diabetes (females 50.3%, mean age 59.9 ± 12.3 years, T2DM 97.3%, duration of diabetes 16.3 ± 9.2 years, baseline BMI 29.9 ± 6.1 kg/m2, baseline HbA1c 8.8 ± 1.6%) were prescribed SGLT2i during the study period. At the time of first SGLT2i prescription, 80.4% used three or more other anti-diabetic agents concomitantly and 34.6% used insulin concomitantly. 151 patients who continue to use at least 6 months were included in analysis. At the last follow-up (median time 16 months), overall median HbA1c reduction and weight reduction were 1.0% and 1.5 kg, respectively. While glycemic control could maintain up to 18 months, weight loss gradually rebounded after the first 6 months and then backed to baseline body weight at 18 months (78.2 ± 18.0 kg vs. 78.0 ± 17.8, p value = 0.324). The incidence of adverse drug reactions of special interest (polyuria, volume depletion-related events, urinary tract infection, genital infection, and hypoglycemia) was 2.1, 1.6, 2.1, 2.6, and 7.9%, respectively.


This real-world study confirmed long-term durability of glycemic control with SGLT2i in not only monotherapy, but also add-on studies with other oral anti-diabetic drugs and/or insulin treatment. However, weight loss became evident early after 6 weeks then reached slightly rebounds after 24 weeks until the end of follow-up. Further studies should be done towards a better understanding of treatment with SGLT2i in routine clinical practice.
NCD Risk Factor Collaboration (NCD-RisC). Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19.2 million participants. Lancet. 2016;387:1377–96. CrossRef
Ali MK, Bullard KM, Saaddine JB, Cowie CC, Imperatore G, Gregg EW. Achievement of goals in US diabetes care, 1999–2010. N Engl J Med. 2013;368:1613–24. CrossRefPubMed
Sieng S, Thinkamrop B, Laohasiriwong W, Hurst C. Comparison of HbA 1c, blood pressure, and cholesterol (ABC) control in type 2 diabetes attending general medical clinics and specialist diabetes clinics in Thailand. Diabetes Res Clin Pract. 2015;108:265–72. CrossRefPubMed
Stratton IM, Adler AI, Neil HAW, Matthews DR, Manley SE, Cull CA, et al. Association of glycemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000;321:405–12. CrossRefPubMedPubMedCentral
List JF, Woo V, Morales E, Tang W, Fiedorek FT. Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes. Diabetes Care. 2009;32:650–7. CrossRefPubMed
Fujita Y, Inagaki N. Renal sodium glucose cotransporter 2 inhibitors as a novel therapeutic approach to treatment of type 2 diabetes: clinical data and mechanism of action. J Diabetes Investig. 2014;5:265–75. CrossRefPubMedPubMedCentral
Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117–28. CrossRefPubMed
Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377:644–57. CrossRefPubMed
Verma S, McMurray JJV, Cherney DZI. The metabolodiuretic promise of sodium-dependent glucose cotransporter 2 inhibition: the search for the sweet spot in heart failure. JAMA Cardiol. 2017;2:939–40. CrossRefPubMed
Scheen AJ, Paquot N. Metabolic effects of SGLT2 inhibitors beyond increased glucosuria: a review of clinical evidence. Diabetes Metab. 2014;40:S4–11. CrossRefPubMed
Cefalu WT, Riddle MC. SGLT2 inhibitors: the latest “new kids on the block”! Diabetes Care. 2015;38:352–4. CrossRefPubMedPubMedCentral
Scheen AJ. SGLT2 inhibitors: benefit/risk balance. Curr Diabetes Rep. 2016;16:92. CrossRef
Rosenstock J, Ferrannini E. Euglycemic diabetic ketoacidosis: a predictable, detectable, and preventable safety concern with SGLT2 inhibitors. Diabetes Care. 2015;38:1638–42. CrossRefPubMed
OgawaW Sakaguchi K. Euglycemic diabetic ketoacidosis induced by SGLT2 inhibitors: possible mechanism and contributing factors. J Diabetes Investig. 2016;7:135–8. CrossRef
Diabetes Association of Thailand. Clinical practice guideline for diabetes 2017. Bangkok: Diabetes Association of Thailand; 2017 (in Thai).
Vasilakou D, Karagiannis T, Athanasiadou E, Mainou M, Liakos A, Bekiari E, et al. Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med. 2013;159:262–74. CrossRefPubMed
Ferrannini E, Mark M, Mayoux E. CV protection in the EMPAREG-OUTCOME trial: a “thrifty substrate” hypothesis. Diabetes Care. 2016;39:1108–14. CrossRefPubMed
Liu XY, Zhang N, Chen R, Zhao JG, Yu P. Efficacy and safety of sodium glucose cotransporter 2 inhibitors in type 2 diabetes: a meta-analysis of randomized controlled trials for 1 to 2 years. J Diabetes Complicat. 2015;29:1295–303. CrossRefPubMed
Tahrani AA, Barnett AH, Bailey CJ. SGLT inhibitors in management of diabetes. Lancet Diabetes Endocrinol. 2013;1:140–51. CrossRefPubMed
Ferrannini E, Muscelli E, Frascerra S, Baldi S, Mari A, Heise T, et al. Metabolic response to sodium glucose cotransporter 2 inhibition in type 2 diabetic patients. J Clin Investig. 2014;124:499–508. CrossRefPubMedPubMedCentral
Kashiwagi A, Yoshida S, Nakamura I, Kazuta K, Ueyama E, Takahashi H, et al. Efficacy and safety of ipragliflozin in Japanese patients with type 2 diabetes stratified by body mass index: a subgroup analysis of five randomized clinical trials. J Diabetes Investig. 2016;7:544–54. CrossRefPubMedPubMedCentral
McGovern A, Feher M, Munro N, de Lusignan S. Sodium-glucose co-transporter 2 (SGLT2) inhibitor: comparing trial data and real-world use. Diabetes Ther. 2017;8:365–76. CrossRefPubMedPubMedCentral
Fitchett D. SGLT2 inhibitors in the real world: too good to be true? Lancet Diabetes Endocrinol. 2017;5:673–5. CrossRefPubMed
Merovci A, Solis-Herrera C, Daniele G, Eldor R, Fiorentino TV, Tripathy D, et al. Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production. J Clin Investig. 2014;124:509–14. CrossRefPubMedPubMedCentral
Abdul-Ghani M. Where dose combination therapy with SGLT2 inhibitor plus a DPP-4 inhibitor fit in the management of type 2 diabetes? Diabetes Care. 2015;38:373–5. CrossRefPubMed
Rosenstock J, Hansen L, Zee P, Li Y, Cook W, Hirshberg B, et al. 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. 2015;38:376–83. CrossRefPubMed
Søfteland E, Meier JJ, Vangen B, Toorawa R, Maldonado-Lutomirsky M, Broedl UC. Empagliflozin as add-on therapy in patients with type 2 diabetes inadequately controlled with linagliptin and metformin: a 24-week randomized, double-blind, parallel-group trial. Diabetes Care. 2017;40:201–9. CrossRefPubMed
Yabe D, Nishikino R, Kaneko M, Iwasaki M, Seino Y. Short-term impacts of sodium/glucose co-transporter 2 inhibitors in Japanese clinical practice: considerations for their appropriate use to avoid serious adverse events. Expert Opin Drug Saf. 2015;14:795–800. CrossRefPubMed
John M, Cerdas S, Violante R, Deeroochanawong C, Hassanein M, Slee A, et al. Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus living in hot climates. Int J Clin Pract. 2016;70:775–85. CrossRefPubMedPubMedCentral
Umpierrez GE. Diabetes: SGLT2 inhibitors and diabetic ketoacidosis—a growing concern. Nat Rev Endocrinol. 2017;13:441–2. CrossRefPubMed
US Food and Drug Administration. Drug safety communications: FDA warns that SGLT2 inhibitors for diabetes may result in a serious condition of too much acid in the blood. http://​www.​fda.​gov/​downloads/​Drugs/​DrugSafety/​UCM446954.​pdf. Accessed 22 Aug 2017.
European Medicines Agency. Review of diabetes medicines called SGLT2 inhibitors started: risk of diabetic ketoacidosis to be examined. EMA. http://​www.​ema.​europa.​eu/​docs/​en_​GB/​document_​library/​Referrals_​document/​SGLT2_​inhibitors_​_​20/​Procedure_​started/​WC500187926.​pdf. Accessed 22 Aug 2017.
Hayami T, Kato Y, Kamiya H, Kondo M, Naito E, Sugiura Y, et al. Case of ketoacidosis by a sodium-glucose cotransporter 2 inhibitor in a diabetic patient with a low-carbohydrate diet. J Diabetes Investig. 2015;6:587–90. CrossRefPubMedPubMedCentral
Yabe D, Iwasaki M, Kuwata H, Haraguchi T, Hamamoto Y, Kurose T, et al. Sodium-glucose co-transporter-2 inhibitor use and dietary carbohydrate intake in Japanese individuals with type 2 diabetes: a randomized, open-label, 3-arm parallel comparative, exploratory study. Diabetes Obes Metab. 2017;19:739–43. CrossRefPubMedPubMedCentral
Aekplakorn W, Satheannoppakao W, Putwatana P, Taneepanichkul S, Kessomboon P, Chongsuvivatwong V, et al. Dietary pattern and metabolic syndrome in Thai adults. J Nutr Metab. 2015;2015:468759. CrossRefPubMedPubMedCentral
Birkeland KI, Jorgensen ME, Carstensen B, Persson F, Gulseth HL, Thuresson M, et al. Cardiovascular mortality and morbidity in patients with type 2 diabetes following initiation of sodium-glucose co-transporter-2 inhibitors versus other glucose-lowering drugs (CVD-REAL Nordic): a multinational observational analysis. Lancet Diabetes Endocrinol. 2017;5:709–11. CrossRefPubMed
Berhan A, Barker A. Sodium glucose co-transport 2 inhibitors in the treatment of type 2 diabetes mellitus: a meta-analysis of randomized double-blind controlled trials. BMC Endocr Disord. 2013;13:58. CrossRefPubMedPubMedCentral

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 »