# Comparative Effectiveness of Two Initial Combination Therapies in Patients with New Onset Diabetes

> **NIH DK R01** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2026 · $684,914

## Abstract

Project Summary/Abstract
The current ADA/EASD recommendation for glucose control in newly diagnosed T2DM patients
who are free from CVD and renal disease is to start on metformin and sequentially add other
glucose lowering agents upon metformin failure to maintain HbA1c <7.0%. The recently
completed GRADE study, which had tested the efficacy of 4 glucose lowering agents (sitagliptin,
glimepiride, liraglutide and glargine insulin) in maintaining the treatment goal in metformin failing
T2DM patients, has demonstrated that the vast majority (67-75%) failed to maintain the treatment
goal at 5 years, suggesting of inability of sequential add on approach on maintaining durable
reduction in the HbA1c.
Initial combination therapy is an alternative therapeutic approach for glucose control in T2DM
patients. The VERIFY study has demonstrated that subjects initiated on combination of metformin
plus vildagliptin had 26% lower failure rate than subjects started on metformin and had vildagliptin
added in metformin-failing subjects. Nonetheless, 43% of subjects receiving initial combination of
metformin plus vildagliptin failed to maintain HbA1c <7.0% at 5 years.
We have demonstrated in EDICT study that, initial combination therapy with agents that correct
known pathophysiologic defects present in T2DM will produce durable reduction in the HbA1c.
Initial combination with pioglitazone plus exenatide BID produced long lasting reduction in the
HbA1c in patients with T2DM and 68% of subjects maintained HbA1c <6.5% at 6 years.
Nonetheless, this combination had some limitations. Approximately, one third of subjects failed to
maintain the treatment goal and bone mineral density has decreased in women > 50 years. These
limitations can be avoided by using dual GLP-1 /GIP agonist in combination with pioglitazone.
Thus, the present study is a comparative effectiveness study comparing the efficacy and durability
of HbA1c reduction by two initial combination therapies, one therapy (pioglitazone

## Key facts

- **NIH application ID:** 11291307
- **Project number:** 5R01DK097554-13
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** Muhammad  Abdul-Ghani
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** DK
- **Fiscal year:** 2026
- **Award amount:** $684,914
- **Award type:** 5
- **Project period:** 2012-09-21T00:00:00 → 2029-02-28T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11291307

## Citation

> US National Institutes of Health, RePORTER application 11291307, Comparative Effectiveness of Two Initial Combination Therapies in Patients with New Onset Diabetes (5R01DK097554-13). Retrieved via AI Analytics 2026-05-18 from https://api.ai-analytics.org/grant/nih/11291307. Licensed CC0.

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