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September 22, 2022

EASD 2022: interactions between DPP-4Is and HbA1c variability in type 2 diabetes

Data have shown that the early initiation of DPP-4Is may delay the need for insulin in T2D patients with low HbA1c variability.

By GlobalData Healthcare

At the 58th Annual European Association for the Study of Diabetes (EASD) meeting in Stockholm, new results were presented from a Hong Kong-based study that demonstrates that the early initiation of dipeptidyl peptidase-4 inhibitors (DPP-4Is) may delay the need for insulin in type 2 diabetes (T2D) patients with low HbA1c variability. The decreased or delayed use of insulin in T2D patients is likely to preserve beta-cell function and maintain, to some extent, the natural secretion of insulin for a longer time period.

Insufficient insulin secretion and non-suppression of glucagon are key features of T2D. DPP-4Is inhibit the degradation of glucagon-like peptide-1 (GLP-1), which suppresses glucagon and augments prandial insulin secretion. It has been previously observed that when using the combination approach of metformin and DPP-4I, there is a reduced need for treatment escalation and a delayed requirement for insulin. Without such an intervention during the early stage of T2D, glycaemic variability (GV) might accelerate the loss of β-cells and worsen glycaemic control.

For this study, the investigators used a territory-wide, population-based prospective cohort that included 103,744 patients with T2D initiated on DPP-4Is. Patients who were treated with insulin at baseline were excluded, as were patients with less than five HbA1c measurements during the follow-up. A one-year period before the first date of dispensing the DPP-4Is was established as the baseline and the insulin requirement was defined as a continuous insulin treatment for at least six months during the follow-up.

From 24,147 patients (53.3% men, age: 63.9 ± 11.6 years, HbA1c: 8.3 ± 1.3%, diabetes duration: 12.3 ± 7.1 years) who fulfilled the inclusion criteria, 90.1% and 87.4% were treated with metformin and sulphonylureas at baseline. During a mean follow-up period of 4.1 years, 20.6% required insulin treatment. Early initiation of treatment with DPP-4Is was associated with a reduced risk of insulin requirement compared to late initiation, with a hazard ratio (HR) of 0.71 (95% confidence interval [CI] 0.66–0.77). The data demonstrate that early initiation of DPP-4Is might delay the requirement for insulin and preserve β-cell function.

DPP-4Is have seen a decrease in their market share across the global T2D market, as both sodium-glucose co-transporter-2 (SGLT-2) inhibitors and GLP-1 receptor agonists (GLP1 RAs) erode DPP-4I market share. This is due to significant volumes of clinical data supporting the use of GLP-1 RAs in T2D, obesity and cardiovascular risk, while SGLT-2 inhibitors are beneficial in heart failure (HF) and chronic kidney disease (CKD).

However, the majority of this shift in prescribing towards the SGLT-2 inhibitors and GLP-1 RAs can be observed in the US market, whereas in the 5EU (France, Germany, Italy, Spain and the UK) and major Asia-Pacific (APAC) markets such as Japan, India and China, there is still a prescribing bias towards DPP-4Is. This is particularly the case for elderly patients, as SGLT-2 inhibitors have had significant label warnings regarding cardiovascular and circulatory adverse events, causing physicians to decrease their prescribing of this class.

Furthermore, several blockbuster DPP-4Is, including the Januvia, Onglyza and Tradjenta franchises, are approaching patent expiries, which will lead to the increase in the market entry of generic equivalents and increase in patient access to these drugs due to the reduced cost and greater availability. In addition, combination therapies, such as Trijardy (empagliflozin + linagliptin + metformin) will likely increase compliance and treatment efficacy, leading physicians to prescribe the therapy and contribute to the continued use of DPP-4Is.

Although increasing competition exists from the GLP-1 RA and SGLT-2 inhibitor classes, GlobalData predicts that positive data regarding DPP-4Is is likely to ensure the continued use of the drugs from this class, and that these drugs will continue to maintain a competitive market share in T2D.

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