An Analysis of EDICT Study: Insulin Secretion Predicts the Need of Insulin Therapy in New-onset T2DM Patients with Poor Glycemic Control

28 Jul, 21

Introduction

Amongst type-2 diabetes mellitus (T2DM) patients with poor glycemic control [glycosylated hemoglobin (HbA1c) >10%], the residual ?-cell function influences the response to antidiabetic therapy.

Aim

To identify predictors of response to glucose-lowering therapy in patients with new-onset T2DM and very high HbA1c (>10%) at baseline

Patient Profile

Participants from the EDICT (Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes) study
All the study subjects had new onset T2DM (duration <2 years; age 18-75 years), were treatment na?ve and had an initial HbA1c >10%

Methods

Study Design

A post hoc analysis of the EDICT study
EDICT was an open-label, randomized controlled trial

Treatment Strategy

All subjects (N = 104) underwent a 75-g oral glucose tolerance test (OGTT) before treatment initiation
Patients were randomized to receive either of the following treatments:

Triple Therapy: Initial triple therapy with metformin, pioglitazone and exenatide (n=49)
Conventional Therapy: Stepwise conventional therapy with metformin (1000 mg/day) followed by glipizide and then insulin glargine to achieve HbA1c <6.5% as follows (n=55):

In case fasting plasma glucose (FPG) at one month was >110 mg/dL or HbA1c was >6.5%, the dose of metformin was increased to 2000 mg/day and glipizide was added at 5 mg/day.
In case FPG was >110 mg/dL or HbA1c was >6.5% at two months, the dose of glipizide was increased to 10 mg/day and then to 20 mg/day.
In case FPG >110 mg/dL or HbA1c >6.5% at three months, glargine insulin was initiated at 10 units before breakfast and escalated weekly by 1-5 units based on the FPG and HbA1c to 60 units/day to maintain FPG at less than <110 mg/dL.

Outcomes

Insulin secretion and insulin resistance as calculated based on the OGTT-derived indices

Results

The mean baseline HbA1c (11.3% vs. 11.2%), FPG (247 mg/dL vs. 255 mg/dL) and disease duration (3.2 months vs. 4.4 months) did not differ significantly between the conventional and the triple therapy groups.
Greater proportion of patients treated with the triple therapy vs. the conventional therapy achieved HbA1c <6.5% at six months (78% vs. 61%), though the difference was statistically insignificant (Table 1).

Table 1: Improvement in HbA1c in the study groups during the study period

Duration	Conventional Group (n=49)	Triple Therapy Group (n=55)
HbA1c at Baseline	11.3%	11.2%
HbA1c at 1 Month	9.4%	9.6%
HbA1c at 3 Months	6.9%	7.3%
HbA1c at 6 Months	6.4%	6.1%

Greater proportion of patients in the conventional treatment group rather than those in the triple therapy group required insulin injection (53% vs. 22%; p=0.001)
Subjects who achieved the HbA1c goal of <6.5% without insulin therapy had a significantly higher insulin secretion (as measured with ?CPEP_0-120) as compared with those who required insulin.
Irrespective of the assigned treatment (conventional or triple therapy) and FPG, insulin secretion at baseline was the strongest predictor of subjects who did not require insulin therapy; a cut-off point of CPEP₁₂₀/CPEP₀(the ratio between plasma C-peptide concentration at 120 minutes during the OGTT and fasting plasma C-peptide concentration) of more than 1.7 predicted subjects who achieved the treatment target without insulin.
Furthermore, subjects with a CPEP₁₂₀/CPEP₀ <1.7 and FPG ≤269 mg/dL also achieved the treatment goal with triple therapy, without the need of insulin administration.

Conclusions

Nearly two-thirds of the newly diagnosed, drug-na?ve T2DM patients with HbA1c >10% and symptoms of hyperglycemia (such as weight loss), achieved good glycemic control during the study without the need for insulin therapy
Insulin secretion in response to a 75-g OGTT predicted the need for insulin therapy at the time of T2DM diagnosis, irrespective of the antidiabetic treatment.
A cut-off of 1.7 of CPEP₁₂₀/CPEP₀ is a valuable clinical tool to individualize glucose-lowering therapy in patients with new-onset T2DM and HbA1c >10%.

Diabetes Obes Metab. 2021;23:1631–1639.