Comparing Effectiveness and Safety of SGLT2 Inhibitors vs DPP-4 Inhibitors in Patients With Type 2 Diabetes and Varying Baseline HbA1c Levels

Key Points Question Does the effectiveness and safety of sodium-glucose cotransporter 2 inhibitors (SGLT2i) differ from that of dipeptidyl peptidase 4 inhibitors (DPP-4i) in patients with type 2 diabetes (T2D) overall and at varying baseline hemoglobin A1c (HbA1c) levels? Findings In this large new-user comparative effectiveness and safety research study including 87 274 propensity-scored matched adults with T2D, SGLT2i treatment initiators had a reduced risk of major cardiovascular events, heart failure, and acute kidney injury and an increased risk of genital infections and diabetic ketoacidosis compared with DPP-4i treatment initiators, regardless of their baseline HbA1c level. Meaning Despite concern that use of SGLT2i at higher HbA1c levels would cause excess risk, the findings of this study suggest that patients with T2D can benefit from the use of SGLT2i regardless of glycemic control, with the expected adverse effect profile when compared with DPP-4i, with no additional risk of adverse effects in patients with elevated HbA1c levels.

[1]  Akshay S. Desai,et al.  Time to Clinical Benefit of Dapagliflozin in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction , 2022, JAMA cardiology.

[2]  Seoyoung C. Kim,et al.  Accuracy of identifying diagnosis of moderate to severe chronic kidney disease in administrative claims data , 2021, Pharmacoepidemiology and drug safety.

[3]  J. Bonventre,et al.  SGLT2 Inhibitors and the Risk of Acute Kidney Injury in Older Adults With Type 2 Diabetes. , 2021, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[4]  Phyo T. Htoo,et al.  Sodium–Glucose Cotransporter-2 Inhibitors Versus Glucagon-like Peptide-1 Receptor Agonists and the Risk for Cardiovascular Outcomes in Routine Care Patients With Diabetes Across Categories of Cardiovascular Disease , 2021, Annals of Internal Medicine.

[5]  N. Powe,et al.  New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race. , 2021, The New England journal of medicine.

[6]  C. Hung,et al.  The efficacy and safety of novel classes of glucose-lowering drugs for cardiovascular outcomes: a network meta-analysis of randomised clinical trials , 2021, Diabetologia.

[7]  T. Imamura,et al.  Relationship Between HbA1c Level and Effectiveness of SGLT2 Inhibitors in Decompensated Heart Failure Patients with Type 2 Diabetes Mellitus. , 2021, International heart journal.

[8]  J. Franklin,et al.  Prevalence of Avoidable and Bias‐Inflicting Methodological Pitfalls in Real‐World Studies of Medication Safety and Effectiveness , 2021, Clinical pharmacology and therapeutics.

[9]  S. Schneeweiss,et al.  Effectiveness and safety of empagliflozin in routine care patients: Results from the EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study , 2021, Diabetes, obesity & metabolism.

[10]  Lawrence A Leiter,et al.  Time to cardiovascular benefits of empagliflozin: a post hoc observation from the EMPA‐REG OUTCOME trial , 2021, ESC heart failure.

[11]  D. Moga,et al.  How well can we assess the validity of non-randomised studies of medications? A systematic review of assessment tools , 2021, BMJ Open.

[12]  P. Ponikowski,et al.  Time to Clinical Benefit of Dapagliflozin and Significance of Prior Heart Failure Hospitalization in Patients With Heart Failure With Reduced Ejection Fraction. , 2021, JAMA cardiology.

[13]  S. Schneeweiss,et al.  Comparative Effectiveness and Safety of Sodium–Glucose Cotransporter 2 Inhibitors Versus Glucagon-Like Peptide 1 Receptor Agonists in Older Adults , 2021, Diabetes Care.

[14]  G. Filippatos,et al.  Effect of Empagliflozin on the Clinical Stability of Patients With Heart Failure and a Reduced Ejection Fraction , 2020, Circulation.

[15]  C. Cannon,et al.  Cardiovascular Outcomes with Ertugliflozin in Type 2 Diabetes. , 2020, The New England journal of medicine.

[16]  L. Lix,et al.  Sodium glucose cotransporter 2 inhibitors and risk of major adverse cardiovascular events: multi-database retrospective cohort study , 2020, BMJ.

[17]  G. Giannelli,et al.  Generalizability of sodium-glucose co-transporter-2 inhibitors cardiovascular outcome trials to the type 2 diabetes population: a systematic review and meta-analysis , 2020, Cardiovascular Diabetology.

[18]  A. Kesselheim,et al.  Heterogeneity of antidiabetic treatment effect on the risk of major adverse cardiovascular events in type 2 diabetes: a systematic review and meta-analysis , 2020, Cardiovascular Diabetology.

[19]  J. Garber,et al.  CONSENSUS STATEMENT BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY ON THE COMPREHENSIVE TYPE 2 DIABETES MANAGEMENT ALGORITHM - 2020 EXECUTIVE SUMMARY. , 2020, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[20]  M. Kanbay,et al.  Renal physiology of glucose handling and therapeutic implications , 2020, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[21]  C. Mathieu,et al.  2019 Update to: Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) , 2019, Diabetes Care.

[22]  J. Curtis,et al.  The Design and Validation of a New Algorithm to Identify Incident Fractures in Administrative Claims Data , 2019, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[23]  S. Arnold,et al.  Eligibility of patients with type 2 diabetes for sodium‐glucose co‐transporter‐2 inhibitor cardiovascular outcomes trials: An assessment using the Diabetes Collaborative Registry , 2019, Diabetes, obesity & metabolism.

[24]  Deepak L. Bhatt,et al.  Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes , 2019, The New England journal of medicine.

[25]  M. Kulldorff,et al.  Empagliflozin and the Risk of Heart Failure Hospitalization in Routine Clinical Care. , 2018, Circulation.

[26]  S. Schneeweiss,et al.  Comparative risk of genital infections associated with sodium‐glucose co‐transporter‐2 inhibitors , 2018, Diabetes, obesity & metabolism.

[27]  R. Herings,et al.  How representative of a general type 2 diabetes population are patients included in cardiovascular outcome trials with SGLT2 inhibitors? A large European observational study , 2019, Diabetes, obesity & metabolism.

[28]  Susan Gruber,et al.  Relative Performance of Propensity Score Matching Strategies for Subgroup Analyses , 2018, American journal of epidemiology.

[29]  Kenneth Rockwood,et al.  Measuring Frailty in Medicare Data: Development and Validation of a Claims-Based Frailty Index , 2018, The journals of gerontology. Series A, Biological sciences and medical sciences.

[30]  S. Schneeweiss,et al.  Cardiovascular outcomes associated with canagliflozin versus other non-gliflozin antidiabetic drugs: population based cohort study , 2018, British Medical Journal.

[31]  B. Carstensen,et al.  Dapagliflozin is associated with lower risk of cardiovascular events and all‐cause mortality in people with type 2 diabetes (CVD‐REAL Nordic) when compared with dipeptidyl peptidase‐4 inhibitor therapy: A multinational observational study , 2017, Diabetes, obesity & metabolism.

[32]  K. Hallow,et al.  Model‐Based Evaluation of Proximal Sodium Reabsorption Through SGLT2 in Health and Diabetes and the Effect of Inhibition With Canagliflozin , 2018, Journal of clinical pharmacology.

[33]  S. Suissa.  Lower Risk of Death With SGLT2 Inhibitors in Observational Studies: Real or Bias? , 2017, Diabetes Care.

[34]  J. Udell,et al.  Sodium Glucose Cotransporter-2 Inhibition in Heart Failure: Potential Mechanisms, Clinical Applications, and Summary of Clinical Trials , 2017, Circulation.

[35]  K. Mahaffey,et al.  Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes , 2017, The New England journal of medicine.

[36]  S. Schneeweiss,et al.  Risk of Diabetic Ketoacidosis after Initiation of an SGLT2 Inhibitor. , 2017, The New England journal of medicine.

[37]  K. Khunti,et al.  Lower Risk of Heart Failure and Death in Patients Initiated on SGLT-2 Inhibitors Versus Other Glucose-Lowering Drugs: The CVD-REAL Study , 2017 .

[38]  Björn Eliasson,et al.  Mortality and Cardiovascular Disease in Type 1 and Type 2 Diabetes , 2017, The New England journal of medicine.

[39]  W. Cefalu,et al.  An update on sodium-glucose co-transporter-2 inhibitors for the treatment of diabetes mellitus , 2016, Current opinion in endocrinology, diabetes, and obesity.

[40]  John M Lachin,et al.  Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. , 2016, The New England journal of medicine.

[41]  B. Zinman,et al.  Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. , 2015, The New England journal of medicine.

[42]  W. Cushman,et al.  Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE: a multicentre, randomised, double-blind trial , 2015, The Lancet.

[43]  Deepak L. Bhatt,et al.  Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. , 2013, The New England journal of medicine.

[44]  Jerry H. Gurwitz,et al.  A systematic review of validated methods for identifying heart failure using administrative data , 2012, Pharmacoepidemiology and drug safety.

[45]  W. Bobo,et al.  Positive predictive value of automated database records for diabetic ketoacidosis (DKA) in children and youth exposed to antipsychotic drugs or control medications: a tennessee medicaid study , 2011, BMC medical research methodology.

[46]  Sebastian Schneeweiss,et al.  A combined comorbidity score predicted mortality in elderly patients better than existing scores. , 2011, Journal of clinical epidemiology.

[47]  Sebastian Schneeweiss,et al.  Validation of claims‐based diagnostic and procedure codes for cardiovascular and gastrointestinal serious adverse events in a commercially‐insured population , 2010, Pharmacoepidemiology and drug safety.

[48]  P. Austin.  Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples , 2009, Statistics in medicine.

[49]  Sushrut S Waikar,et al.  Validity of International Classification of Diseases, Ninth Revision, Clinical Modification Codes for Acute Renal Failure. , 2006, Journal of the American Society of Nephrology : JASN.

[50]  Sebastian Schneeweiss,et al.  Accuracy of Medicare claims-based diagnosis of acute myocardial infarction: estimating positive predictive value on the basis of review of hospital records. , 2004, American heart journal.

[51]  W. Longstreth,et al.  Validating Administrative Data in Stroke Research , 2002, Stroke.

[52]  E. Wagner,et al.  The use of automated data to identify complications and comorbidities of diabetes: a validation study. , 1999, Journal of clinical epidemiology.