Comparative effectiveness and safety of sodium-glucose cotransporter-2 inhibitors versus metformin in patients with type 2 diabetes: An observational study using data from routine care.
SGLT2 inhibitor
antidiabetic drug
cohort study
metformin
type 2 diabetes
Journal
Diabetes, obesity & metabolism
ISSN: 1463-1326
Titre abrégé: Diabetes Obes Metab
Pays: England
ID NLM: 100883645
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
revised:
03
06
2021
received:
25
03
2021
accepted:
18
06
2021
pubmed:
26
6
2021
medline:
21
10
2021
entrez:
25
6
2021
Statut:
ppublish
Résumé
To assess the effectiveness and safety of sodium-glucose cotransporter-2 (SGLT2) inhibitors in treatment-naïve patients compared with metformin. We conducted a cohort study of US adults with type 2 diabetes mellitus who had not filled a prescription for a diabetes medication in the preceding year. We then identified patients who newly filled a prescription for an SGLT2 inhibitor or metformin between 2013 and 2018. The primary outcome was a composite of heart failure, myocardial infarction or stroke. Safety outcomes included hypoglycaemia, diabetic ketoacidosis, genital infection, lactic acidosis and acute kidney injury. After 1:1 propensity-score (PS) matching, proportional hazards models were fit to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). We identified 9964 individuals newly prescribed an SGLT2 inhibitor who were PS-matched to 9964 individuals newly prescribed metformin. The mean age was 54 years, 52% were women, and the duration of follow-up was 213 days for metformin and 147 days for SGLT2 inhibitors. The primary outcome occurred in 54 patients (7.2 events per 1000 person-years) who received an SGLT2 inhibitor, compared to 84 patients (8.5 per 1000 person-years) who received metformin (HR 0.82, 95% CI 0.58, 1.15). Similar results (HR 0.87, 95% CI 0.69, 1.09) were observed in an analysis with longer follow-up (ie, approximately 600 days). The rates of genital infection (HR 2.28, 95% CI 1.87, 2.78) and diabetic ketoacidosis (HR 1.58, 95% CI 0.92, 2.70) were higher for patients prescribed an SGLT2 inhibitor compared to metformin, while the rates of acute kidney injury (HR 0.94, 95% CI 0.60, 1.47) or hypoglycaemia (HR 0.83, 95% CI 0.48, 1.42) were not. We observed a numerically lower rate of short-/mid-term cardiovascular events for patients newly prescribed an SGLT2 inhibitor compared to metformin, albeit with wide CIs that include the possibility of a null effect. SGLT2 inhibitors were associated with a higher rate of genital infection and diabetic ketoacidosis. Larger cohort studies and long-term clinical trials powered to assess cardiovascular events are necessary to understand the risk-benefit profile of SGLT2 inhibitors as first-line therapy for adults with type 2 diabetes mellitus.
Substances chimiques
Hypoglycemic Agents
0
Sodium-Glucose Transporter 2 Inhibitors
0
Metformin
9100L32L2N
Sodium
9NEZ333N27
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Observational Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2320-2328Subventions
Organisme : NIA NIH HHS
ID : K08 AG055670
Pays : United States
Organisme : CIHR
Pays : Canada
Informations de copyright
© 2021 John Wiley & Sons Ltd.
Références
Cheng AYY. Introduction. Canadian Journal of Diabetes. 2013;37:S1-S3. https://doi.org/10.1016/j.jcjd.2013.01.009.
Chamberlain JJ, Herman WH, Leal S, et al. Pharmacologic therapy for type 2 diabetes: synopsis of the 2017 American Diabetes Association standards of medical care in diabetes. Ann Intern Med Ann. 2017;1667326(10):572-578.
Inzucchi SE. Is it time to change the type 2 diabetes treatment paradigm? No! metformin should remain the foundation therapy for type 2 diabetes. Diabetes Care. 2017;40(8):1128-1132.
Maruthur NM, Tseng E, Hutfless S, et al. Diabetes medications as monotherapy or metformin-based combination therapy for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med. 2016;164(11):740-751.
Turner RC, Cull CA, Frighi V, Holman RR, for the UK Prospective Diabetes Study (UKPDS) Group. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). JAMA. 1999;281(21):2005-2012. https://doi.org/10.1001/jama.281.21.2005.
Griffin SJ, Leaver JK, Irving GJ. Impact of metformin on cardiovascular disease: a meta-analysis of randomised trials among people with type 2 diabetes. Diabetologia. 2017;60(9):1620-1629.
UK Prospective Diabetes Study. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK prospective diabetes study (UKPDS) group. Lancet. 1998;352:854-865.
Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377(7):644-657.
Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117-2128.
Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019;380(4):347-357.
Bolen S, Feldman L, Vassy J, Wilson L, Yeh H. Review annals of internal medicine systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus. Ann Intern Med. 2007;147:386-399.
Wu JHY, Foote C, Blomster J, et al. Effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular events, death, and major safety outcomes in adults with type 2 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2016;4(5):411-419.
Goldberg N, Fralick M. Sodium - glucose cotransporter 2 inhibitors for treating diabetes mellitus. CMAJ. 2017;189:E724.
Rosenstock J, Chuck L, González-Ortiz M, et al. Initial combination therapy with canagliflozin plus metformin versus each component as monotherapy for drug-naïve type 2 diabetes. Diabetes Care. 2016;39(3):353-362.
Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019;380(24):2295-2306.
McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381(21):1995-2008.
Packer M, Anker SD, Butler J, et al. Cardiovascular and renal outcomes with Empagliflozin in heart failure. N Engl J Med. 2020;383(15):1413-1424.
Hedrington MS, Davis SN. The role of empagliflozin in the management of type 2 diabetes by patient profile. Ther Clin Risk Manag. 2015;11:739-749.
Fralick M, Kesselheim AS, Avorn J, Schneeweiss S. Use of health care databases to support supplemental indications of approved medications. JAMA Intern Med. 2018;178(1):55-63.
Schneeweiss S. A basic study design for expedited safety signal evaluation based on electronic healthcare data. Pharmacoepidemiol Drug Saf. 2010;19(8):858-868.
Patorno E, Gopalakrishnan C, Franklin JM, et al. Claims-based studies of oral glucose-lowering medications can achieve balance in critical clinical variables only observed in electronic health records. Diabetes Obes Metab. 2018;20(4):974-984.
Khokhar B, Jette N, Metcalfe A, et al. Systematic review of validated case definitions for diabetes in ICD-9-coded and ICD-10-coded data in adult populations. BMJ Open. 2016;6(8):e009952. https://doi.org/10.1136/bmjopen-2015-009952.
McCormick N, Lacaille D, Bhole V, Avina-Zubieta JA. Validity of myocardial infarction diagnoses in administrative databases: a systematic review. PLoS One. 2014;9(3):e92286.
McCormick N, Bhole V, Lacaille D, Avina-Zubieta JA. Validity of diagnostic codes for acute stroke in administrative databases: a systematic review. PLoS One. 2015;10(8):e0135834.
McCormick N, Lacaille D, Bhole V, Avina-Zubieta JA. Validity of heart failure diagnoses in administrative databases: a systematic review and meta-analysis. PLoS One. 2014;9(8):e104519.
Rathmann W, Kostev K. Fracture risk in patients with newly diagnosed type 2 diabetes: a retrospective database analysis in primary care. J Diabetes Complications. 2015;29(6):766-770.
Leslie W, Rubin M, Schwartz A, Kanis J. Type 2 diabetes and bone. J Bone Min Res. 2012;27:2231-2237.
Austin PC. Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples. Stat Med. 2009;28:3083-3107.
U.S. Food and Drug Administration (FDA). Empagliflozin drug label. 2018.
U.S. Food and Drug Administration (FDA). Canagliflozin drug label. 2018.
Wang SV, Verpillat P, Rassen JA, Patrick A, Garry EM, Bartels DB. Transparency and reproducibility of observational cohort studies using large healthcare databases. Clin Pharmacol Ther. 2016;99(3):325-332.
Patorno E, Schneeweiss S, Gopalakrishnan C, Martin D, Franklin JM. Using real-world data to predict findings of an ongoing phase IV cardiovascular outcome trial: cardiovascular safety of linagliptin versus glimepiride. Diabetes Care. 2019;42(12):2204-2210.
Wilding J, Fernando K, Milne N, et al. SGLT2 inhibitors in type 2 diabetes management: key evidence and implications for clinical practice. Diabetes Ther. 2018;9:1757-1773.
Fralick M, Schneeweiss S, Patorno E. Risk of diabetic ketoacidosis after initiation of an SGLT2 inhibitor. N Engl J Med. 2017;376(23):2300-2302.
Meyer EJ, Gabb G, Jesudason D. SGLT2 inhibitor-associated Euglycemic diabetic ketoacidosis: a south Australian clinical case series and Australian spontaneous adverse event notifications. Diabetes Care. 2018;dc171721. 41(4):e47-e49. https://doi.org/10.2337/dc17-1721.
Fralick M, Avorn J, Franklin JM, Abdurrob A, Kesselheim AS. Application and impact of run-in studies. J Gen Intern Med. 2018;33(5):759-763.