Progression of glucose-lowering diabetes therapy in TECOS

Abstract

Aims: TECOS was a randomized, double-blind, placebo-controlled trial assessing the impact of sitagliptin vs. placebo on cardiovascular outcomes when added to usual care in patients with type 2 diabetes. We report the use of concomitant diabetes medications and the risk for progression to insulin during follow-up.

Materials and methods: TECOS enrolled 14 671 participants with HbA1c 6.5%-8.0% on monotherapy with metformin, pioglitazone, sulfonylurea (SU), or dual therapy with two oral agents or insulin with or without metformin. Subsequent diabetes management was by the participant's usual care physician. Time to initiation of insulin and risk of hypoglycaemia were estimated using Cox proportional hazards models.

Results: The most common glucose-lowering regimens at baseline were metformin monotherapy (30.2%), SU monotherapy (8.5%), metformin/SU therapy (35.1%), and insulin with or without metformin (13.9% and 8.6%, respectively). Over a median 3.0 years' follow-up, diabetes therapy was intensified in 25.2% of participants (sitagliptin 22.0%, placebo 28.3%). Medications most commonly added were SU (8.3%) or insulin (8.8%). Insulin initiation in the usual care setting occurred at mean (standard deviation) HbA1c of 8.5 (1.5)%. Sitagliptin did not impact rates of severe hypoglycaemia, but delayed progression to insulin when added to metformin or metformin/SU regimens.

Conclusion: Consistent with the trial's pragmatic design, TECOS participants underwent typical progression of diabetes medications. Sitagliptin was associated with lower HbA1c, without increased risk for severe hypoglycaemia and was associated with delayed progression to insulin when added to metformin with or without SU.

Keywords: DPP‐4 inhibitor; hypoglycaemia; insulin; sitagliptin; type 2 diabetes.

Figure 1

Composition of diabetes medication regimen by duration of diabetes. Insulin indicates both short‐ and long‐acting preparations used alone or in combination with other agents

Figure 2

Concomitant diabetes medication added during follow‐up by randomized treatment group (A) overall and (B‐D) according to baseline diabetes medication use. The addition of any antihyperglycaemic agent was permitted by the TECOS protocol, with the exception of GLP‐1 receptor agonists or open‐label DPP‐4 inhibitors. Use of rosiglitazone was discouraged. Hazard ratios, confidence intervals and P‐values are from Cox proportional hazards regression models for the association between randomized treatment and time to addition of the given medication, stratified by region. AGI, alpha‐glucosidase inhibitor; DPP‐4i, dipeptidyl peptidase‐4 inhibitor; GLP‐1 RA, glucagon‐like peptide‐1 receptor agonist; NSS, non‐sulfonylurea secretagogue; SU, sulfonylurea; TZD, thiazolidinedione

Figure 3

Initiation of chronic insulin therapy by randomized treatment group (A) overall and (B‐D) according to baseline diabetes medication use