Sanjay Kalra ( Department of Endocrinology, Bharti Hospital, Karnal, India. )
Saptarshi Bhattacharya ( Department of Endocrinology, Max Hospital, Patparganj, New Delhi, India )
Nitin Kapoor ( Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore (TN) -632004, India, and Non Communicable Disease Unit, Melbourne School of Population and Global Health, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia. )
The availability of newer glucose-lowering drugs has created opportunities for comprehensive diabetes care. Two classes of drugs, GLP1RA (glucagon-like peptide 1 receptor agonists), and SGLT2i (sodium glucose cotransporter 2 inhibitors) have demonstrated their efficacy in glucose control as well as cardiovascular risk reduction. While both can be used together, there is an ongoing debate regarding their relative advantages and limitations. We present a clinical perspective to compare and control these two classes of drugs, and promote rational prescription in diabetes praxis.
Keywords: Canagliflozin, CV risk reduction, dapagliflozin, dulaglutide, empagliflozin, GLP1RA, liraglutide, obesity, semaglutide, SGLT2i.
Contemporary diabetes management guidelines support the use of glucagon-like peptide1 receptor agonists (GLP1RA) and sodium-glucose co-transporter-2 inhibitors (SGLT2i) as front-line agents.1 This is because of the robust evidence related to their glucose lowering efficacy as well as cardiovascular safety and benefits.
Both classes of drugs have different mechanisms of action, pleiotropic benefits and side effect profiles. Recommendations do offer guidance as to which drug class to prefer in patients at risk of heart failure, but do not replace clinical judgment. This brief communication assists physicians in choosing between the two types of drugs. It uses a simple 3x3 table to aid in clinical decision making (Table). It must be noted that both GLP1RA and SGLT2i can be co-administered as well.
Treatment should be matched to the patient's characteristics, needs and wishes; not the other way round. A detailed clinical assessment is essential to understand the expected benefits and possible risks of GLP1RA and/or SGLT2i therapy in an individual patient.
Both drug classes have some common contraindications: type 1 diabetes, childhood/adolescence, pregnancy and lactation. Beyond this, various molecules are contraindicated in specific situations (liraglutide: medullary thyroid carcinoma, multiple endocrine neoplasia 2; SGLT2i: end stage renal disease, active genitourinary infection).2,3
Both GLP1RA and SGLT2i are preferentially indicated in persons with type 2 diabetes and cardiometabolic risk factors.4 The route of administration, need for reduction in appetite, and expected speed of cardiovascular benefit may influence patient preference for one drug over another (Table). Baseline vasculo-metabolic status, including adiposity, lipid profile, risk of heart failure, status of ASCVD and renal function, also modify choice of therapy. Apart from the vasculo-metabolic health, comprehensive medical status influences clinical decision making. Knowledge of potential risk and side effects of a drug, coupled with information about the patient's health profile, allows for rational prescription.5,6
Diabetes therapy is a complex and challenging area of medicine. Newer drugs have expanded choices for patients and for prescribers. These include GLP1RA and SGLT2i, both of which are recommended for use in type 2 diabetes. However, it sometimes becomes difficult to decide which drug class to prefer. We have highlighted simple clinical parameters which assist in this decision making.
1. American Diabetes Association. 6. Glycemic Targets: Standards of Medical Care in Diabetes-2021. Diabetes Care. 2021; 44(Suppl 1): S73-S84.
2. Kalra S, Sahay R. A Review on Semaglutide: An Oral Glucagon-Like Peptide 1 Receptor Agonist in Management of Type 2 Diabetes Mellitus. Diabetes Ther. 2020; 11:1965-82.
3. Kalra S, Shetty KK, Nagarajan VB, Ved JK. Basic and clinical pharmaco-therapeutics of SGLT2 inhibitors: a contemporary update. Diabetes Therapy. 2020; 11:813-33.
4. Gupta Y, Kalra S. Choice of Glucose-lowering Therapy- A Metabolic Fulcrum-based Approach. US Endocrinology. 2015; 11:79.
5. Kalra S, Das AK, Sahay RK, Baruah MP, Tiwaskar M, Das S, et al. Consensus Recommendations on GLP-1 RA Use in the Management of Type 2 Diabetes Mellitus: South Asian Task Force. Diabetes Ther. 2019; 10:1645-717.
6. Kalra S, Bhattacharya S, Kapoor N. Contemporary Classification of Glucagon-Like Peptide 1 Receptor Agonists (GLP1RAs). Diabetes Ther. 2021; 12:2133-2147.