New kids on the block – how the latest pharmaceutical treatments are changing type 2 diabetes care

By Tom Waddell
6th December 2022
Behind the Science, Type 2 diabetes

The pharmaceutical market aimed at tackling type 2 diabetes (T2D) is vibrant, to say the least.

Driven primarily by an increase in global T2D prevalence and a greater market capture of newer (and more expensive) treatment classes, global pharma revenue is projected to double by 2030.

Prescription of Dipeptidyl Peptidase IV inhibitors (DPP4-Is) as a second-line therapy more than doubled between 2010-2017, while prescription of Sodium-Glucose co-transporter-2 inhibitors (SGLT2-Is) constituted 17% of all new first-to fourth-line therapies (1). But what exactly are these newer treatments, and why are they becoming so popular?

In the interest of brevity, SGLT2-I’s work by reducing the amount of glucose reabsorbed by the kidneys (subsequently increasing the amount of glucose excreted in urine), while Glucagon-Like Peptide-1 receptor agonists (GLP1-RAs) and DPP4-Is act on increasing the level of incretin hormones that promote insulin release and appetite suppression.

Although the primary target of such treatments is blood glucose control, results from large clinical trials such as the EMPA-REG OUTCOME study have revealed a plethora of benefits that extend beyond glycaemic control alone.

For example, clinical trials investigating the efficacy of SGTL2-Is and GLP1-RAs in people with T2D have reported notable reductions in major cardiovascular events including myocardial infarction, heart failure and all- cause admission to hospital vs placebo (2) (3). While prescription of SGLT2-Is have shown to slow the rate of kidney function decline and reduce the incidence of major renal outcomes (4).

Furthermore, treatment with GLP1-RAs has reported to significantly reduce measures of liver fat (as derived from magnetic resonance imaging) and promote greater histological resolution of NASH vs placebo (5) (6).

Given the significant concomitance of fatty liver disease and cardiovascular disease in people with T2D, such outcomes are particularly encouraging for tackling the complexity of T2D and burden of secondary complications.

While a full critique of the mechanisms behind such outcomes is beyond the scope of this review, a common theme is the ability of these treatments to elicit significant weight loss.

Results from the STEP 1 clinical trial reported that treatment with Semaglutide – a GLP1-RA – resulted in a 12% greater reduction in body weight vs placebo, and in 2022 NICE made a momentous statement by recommending Semaglutide for managing obesity in adults with ‘at least one weight-related condition and a body mass index of at least 35kg/m2’.

This brief review has only scratched the surface of the literature available on the use of SGTL2-Is and GLP1-RAs for tackling T2D, however I hope it has served to assure you that the hype around these treatments is just. T2D is a truly multi-organ disease, and the encouraging results from various clinical trials are indicating potential multi-organ treatment options in response.

References

  • Dennis, J.M., et al. 2019. Time trends in prescribing of type 2 diabetes drugs, glycemic response and risk factors: a retrospective analysis of primary care data, 2010-2017. Diabetes, obesity & metabolism.
  • McGuire, D.K., et al. 2020. Effects of empagliflozin on first and recurrent clinical events in patients with type 2 diabetes and atherosclerotic cardiovascular disease: a secondary analysis of the EMPA-REG OUTCOME trial.The Lancet Diabetes & Endocrinology.
  • Meier, J.J. and Nitschmann, S., 2017. Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER).INTERNIST.
  • Heerspink, H.J et al. 2020. Kidney outcomes associated with use of SGLT2 inhibitors in real-world clinical practice (CVD-REAL 3): a multinational observational cohort study.The lancet Diabetes & endocrinology.
  • Yan, J., et al. 2019. Liraglutide, sitagliptin, and insulin glargine added to metformin: the effect on body weight and intrahepatic lipid in patients with type 2 diabetes mellitus and nonalcoholic fatty liver disease. Hepatology.
  • Mantovani, A., et al. 2021. Glucagon-like peptide-1 receptor agonists for treatment of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: an updated meta-analysis of randomized controlled trials. Metabolites.

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