# Effects of Short‐Term Intensive Insulin Therapy Combined With Oral Hypoglycemic Agents for Inducing Remission in Newly Diagnosed Type 2 Diabetes Mellitus: A Randomized Clinical Trial

## TL;DR

Combining short-term intensive insulin therapy with oral diabetes drugs improved short-term blood sugar control but did not increase long-term diabetes remission rates.

## Contribution

The study shows that adding oral hypoglycemic agents to intensive insulin therapy improves short-term glycemic control but not long-term remission in new type 2 diabetes patients.

## Key findings

- Combination therapy reduced insulin requirements and improved glycemic control during intensive insulin treatment.
- Short-term glycemic parameters and β-cell function improved with oral agents but did not lead to better 12-month remission rates.
- Similar long-term remission rates suggest prolonged therapy may be needed for sustained benefits.

## Abstract

To investigate the effects of combining oral hypoglycemic agents with short‐term intensive insulin therapy (SIIT) via continuous subcutaneous insulin infusion (CSII) on glycemic outcomes in adults with newly diagnosed type 2 diabetes mellitus.

In this multicenter, open‐label trial, 245 participants were randomized to three treatment arms: SIIT for 2 weeks (CSII group), SIIT plus 90‐day metformin and pioglitazone (CSII + Met + Pio group), or SIIT plus 90‐day sitagliptin (CSII + Sita group). The primary outcome was the 12‐month diabetes remission rate. Parameters of glycemic control, β‐cell function, and insulin resistance were compared among groups.

The participants had a mean HbA1c of 10.6% ± 2.2%. Compared to the CSII group, both combination groups had lower total daily and pre‐meal bolus insulin requirements with higher time in tight target range (TITR) during SIIT, and had significantly greater acute insulin response (AIR) after SIIT. Three months post SIIT, more participants in the CSII + Met + Pio group (78.7%, 59/75) achieved HbA1c < 6.5% compared with the CSII group (59.0%, 46/78; adjusted p < 0.05), but the 12‐month diabetes remission rates were similar (p = 0.972).

Oral hypoglycemic agents facilitated SIIT implementation and enhanced transient improvements in glycemic control. However, similar 12‐month diabetes remission rates suggest prolonged sequential therapy may be needed for sustained glycemic benefit.

A 3‐month regimen of insulin sensitizers (metformin and pioglitazone) or sitagliptin, combined with short‐term intensive insulin therapy (SIIT), promoted tight glycemic control during SIIT period and improved short‐term glycemic parameters and β‐cell function. However, these benefits did not translate into enhanced long‐term diabetes remission. Further studies are warranted to evaluate whether extended sequential therapies targeting insulin resistance and obesity can achieve superior long‐term glycemic control and β‐cell preservation.

The addition of insulin sensitizers (metformin and pioglitazone) or sitagliptin to short‐term intensive insulin therapy (SIIT) facilitated SIIT implementation and enhanced short‐term glycemic control in patients with newly diagnosed type 2 diabetes. However, 12‐month remission rates were similar to SIIT alone, suggesting a need for prolonged therapy.