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Sitagliptin + metformin/sulphonylurea delays progression to chronic insulin therapy in T2D

Audrey Abella
19 Sep 2017
Dr Samuel Engel on the impact of sitagliptin on insulin initiation.

The oral dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin reduced the rates of progression to chronic insulin therapy (a continuous period of insulin use beyond 3 months), in patients with type 2 diabetes (T2D) on metformin or sulphonylurea mono- or dual therapy compared with placebo, according to data presented at EASD 2017.

“[The] rates of progression to insulin [were] highest in those taking metformin plus sulphonylurea,” said Dr Samuel Engel, an endocrinologist from New York, US.

Researchers identified noninsulin users from the TECOS* trial (n=11,263) who were receiving metformin (n=4,435), sulphonylurea (n=1,246), or both (n=5,152). Of these, 1,230 patients were initiated on insulin and randomized to receive sitagliptin (n=83, 69, and 363 in addition to metformin, sulphonylurea, and dual therapy, respectively) or placebo (n=125, 68, and 522, respectively). Median follow up was approximately 3 years. [EASD 2017, abstract 1]

Rates of progression to insulin were reduced among participants receiving sitagliptin vs placebo in addition to metformin (1.3 vs 2.0 events per 100 patient-years, hazard ratio [HR], 0.67; p=0.005) and metformin + sulphonylurea (5.1 vs 7.8 events per 100 patient-years, HR, 0.64; p<0.0001).

Dual therapy appeared superior among the three groups with significant differences emerging as early as the first treatment year and diverging over time, said Engel.

These findings were consistent with the initial TECOS findings revealing a reduced likelihood of starting long-term insulin treatment in sitagliptin vs placebo patients (HR, 0.70; p<0.001). [N Eng J Med 2015;373:232-242]

Drop-in treatment with other antihyperglycaemic agents during follow-ups might have limited the findings, said Engel. Other limitations were the limited insulin alternatives and the well-controlled risk factors in this population. “[E]nrolled mono- and dual therapy participants may not be representative of those requiring progression to insulin,” he added.

It is important to evaluate other treatment alternatives given insulin-associated concerns such as hypoglycaemia and weight gain as well as complexities involved in injection therapy, said Engel. However, there is limited data on the effect of sitagliptin on delaying progression to insulin initiation despite being approved for monotherapy or in combination with insulin or other agents, he added.

Given issues that might influence clinicians’ decisions to initiate insulin therapy, the findings may shed light on the role of sitagliptin as a probable treatment alternative for T2D, noted Engel.

 

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Most Read Articles
Roshini Claire Anthony, 2 days ago

The combined use of piperacillin and tazobactam does not appear to be a suitable alternative to meropenem for patients with bloodstream infections caused by ceftriaxone-resistant Escherichia coli (E. coli) or Klebsiella pneumoniae (K. pneumoniae), according to results of the MERINO* trial.

Tristan Manalac, 5 days ago
Taking oral antibiotics appears to increase the risk of nephrolithiasis, according to a recent study. Moreover, the risk seems to be compounded for individuals with recent antibiotic exposure and those who were exposed at a younger age.
Jairia Dela Cruz, 6 days ago
Male smokers under the age of 50 years are at risk of developing ischaemic stroke, and this risk increases with the number of cigarettes smoked daily, according to data from the Stroke Prevention in Young Men Study.
Yesterday
Early renin-angiotensin-aldosterone system (RAAS) blockade with renin-angiotensin system inhibitors (RASI) leads to better short- and long-term renal outcomes in systemic lupus erythematosus (SLE) patients with antiphospholipid-associated nephropathy (aPLN), according to a study, adding that this renal protective effect is independent of RASI’s antihypertensive and antiproteinuric effects.