A consensus report by the American Diabetes Association (ADA) and the European. Association for the Study of Diabetes (EASD).
GLUCOSE – LOWERING MEDICATION IN TYPE 2 DIABETES : OVERALL APPROACH ESTABLISHED ASCVD OR CKD ASCVD PREDOMINATES EITHER / OR GLP-1 RA with proven CVD benefit (1) SGLT2i with proven CVD benefit (1) if eGFR adequate (2) If HbA1c above target If further intensification is required or patient is now unable to tolerate GLP-1 RA and / or SGLT2i choose agents demonstrating CV safety Consider adding the other class ( GLP-1 RA or SGLT2i ) with proven CV benefit DPP-4i if not on GLP-1 RA Basal insulin (4) TZD (5) SU (6)
HF OR CKD PREDOMINATES-PREFERABLY SGLT2i with evidence of reducing HF and / or CKD progression in CVDTs if eGFR adequate If SGLTi not tolerated or contraindicated or if eGFR less than adequate (2) add GLP-1 RA with proven CVD benefit (1) If HbA1c above target Avoid TZD in setting of HF Consider agents demonstrating CV safety Consider adding the other class with proven CVD benefit (1) DPP-4i ( not saxagliptin ) in the setting of HF ( if not on GLP-1 RA ) Basal insulin (4) SU(6)
Proven CVD benefit means it has label indication of reducing CVD benefits. For GLP-1 RA strongest evidence for liraglutide > semaglutide > exenatide extended release. For SGLT2i evidence modestly stronger for empagliflazocin > canagliflazocin Beware that SGLT2i vary by region and individual agent with regard to indicated level of eGFR for initiation and continued use Both empagliflazocin and canagliflazocin have shown reduction in HF and reduction in CKD progression in CVDTs Degludec or U 100 glargine have demonstrated CVD safety
5 Low dose may be better tolerated though less well studies for CVD effects 6 Choose later generation SU with lower risk of hypoglycemia 7 Degludec / glargine U300 > glargine U100 / detemir < NPH insulin 8 Semaglutide > liraglutide > dulaglutide > exenatide > lixisenatide 9 If no specific comorbidities ( i.e no estabilished CVD , low risk of hypoglycemia and lower priority to avoid weight gain or no weight related comorbidities ) 10 Consider country and region specific cost of drugs. In some countries TZDs relatively more expensive and DPP-4i relatively cheaper
If triple therapy required or SGLT2i and / or GLP-1 RA no tolerated or contraindicated use regimens with lowest risk of weight gain PREFERABLY DPP-4I ( if not on GLP-1 RA ) based on weight neutrality
Reference Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) Melanie J. Davies1,2 & David A. D’Alessio3 & Judith Fradkin4 & Walter N. Kernan5 & Chantal Mathieu6 & Geltrude Mingrone7,8 & Peter Rossing9,10 & Apostolos Tsapas11 & Deborah J. Wexler12,13 & John B. Buse14
This chart has been reproduced with the kind permission of Melanie J Davies CBE MBChB MD FRCP FRCGP FMedSci Professor of Diabetes Medicine NIHR Senior Investigator Emeritus Diabetes Research Centre – Bloom University of Leicester