Expected Health Benefits of SGLT-2 Inhibitors and GLP-1 Receptor Agonists in Older Adults

Abstract

Background. Older and sicker adults with type 2 diabetes (T2D) were underrepresented in randomized trials of glucagon-like peptide 1 receptor-agonist (GLP1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2I), and thus, health benefits are uncertain in this population. Objective. To assess the impact of age, health status, and life expectancy in older adults with T2D on health benefits of GLP1RA and SGLT2I. Design. We used the United Kingdom Prospective Diabetes Study (UKPDS) model to simulate lifetime health outcomes. We calibrated the UKPDS model to improve mortality prediction in older adults using a common geriatric prognostic index. Participants. National Health and Nutrition Examination Survey 2013–2018 participants 65 y and older with T2D, eligible for GLP1RA or SGLT2I according to American Diabetes Association guidelines. Interventions. GLP1RA or SGLT2I use versus no additional medication. Main Measures. Lifetime complications and weighted life-years (LYs) and quality-adjusted life-years (QALYs) across overall treatment arms and life expectancies. Key Results. The overall older adult population was predicted to experience significant health benefits from GLP1RA (+0.29 LY [95% confidence interval: 0.27, 0.31], +0.15 QALYs [0.14, 0.16]) and SGLT2I (+0.26 LY [0.24, 0.28], +0.13 QALYs [0.12, 0.14]) as compared with no added medication. However, expected benefits declined in subgroups with shorter life expectancies. Participants with <4 y of life expectancy had minimal gains of <0.05 LY and <0.03 QALYs from added medication. Accounting for injection-related disutility, GLP1RA use reduced QALYs (−0.03 QALYs [−0.04, −0.02]). Conclusions. While GLP1RA and SGLT2I have substantial health benefits for many older adults with type 2 diabetes, benefits are not clinically significant in patients with <4 y of life expectancy. Life expectancy and patient preferences are important considerations when prescribing newer diabetes medications. Highlights On average, older adults benefit significantly from SGLT2I and GLP1RA use. However, the benefits of these drugs are not clinically significant among older patients with life expectancy less than 4 y. There is potential harm in injectable GLP1RA use in the oldest categories of adults with type 2 diabetes. Heterogeneity in life expectancy and patient preferences for injectable versus oral medications are important to consider when prescribing newer diabetes medications

Individualizing Care for Older Adults With Diabetes Amid the Revolution in Pharmacotherapy

“…When accounting for the additional negative experience of routine injections, GLP1RAs actually reduced QOL. 10 Thus, the overall QOL impact of a treatment, even those with considerable benefits, can be negative if life expectancy is short and drug delivery causes discomfort.…”

“…In a decision analytic study assessing the impact of life expectancy on treatment benefits of adding GLP1RAs and SGLT2Is, participants with less than 4 years of life expectancy had minimal gains in quality of life (QOL) from these medications. When accounting for the additional negative experience of routine injections, GLP1RAs actually reduced QOL . Thus, the overall QOL impact of a treatment, even those with considerable benefits, can be negative if life expectancy is short and drug delivery causes discomfort.…”

New Developments in Pharmacological Treatment of Obesity and Type 2 Diabetes—Beyond and within GLP-1 Receptor Agonists

“…These effects may partially contribute to the cardioprotective effects of agents targeting the incretin axis, particularly in the context of heart failure. Furthermore, GLP-1 receptor agonists have been demonstrated to exert a protective effect on the microvascular compartment of the myocardium [ 46 , 47 ]. Substantial evidence also supports the beneficial effects of the GLP-1 hormone on epicardial adipose tissue [ 48 ] and in the treatment of metabolic-associated fatty liver disease (MAFLD—formerly known as non-alcoholic fatty liver disease) [ 49 ].…”