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Which Oral Meds Are Best At Reducing HbA1c?

Oct 29, 2019
Editor: David L. Joffe, BSPharm, CDE, FACA

Author: Hira Gohar, Florida A&M University, College of Pharmacy, PharmD Candidate

Data from this study shows the effects of oral diabetes medications on reducing HbA1C levels from two separate cohort groups.

At the moment, metformin is still the first line therapy for most patients who are diagnosed with type 2 diabetes. It is definitely important to explore other oral diabetes medications because metformin does not prove effective for everyone. This study compares four different oral diabetes medications to help health care providers can make their best efforts in understanding which oral medication is best for reducing HbA1C in patients with uncontrolled diabetes.


This is an interventional randomized clinical trial that is in direct correlation with a Scotland-wide study on the “Response to Oral Agents in Diabetes” (ROAD). This study is divided into two cohorts, one of which focuses on patients who are placed on four specific oral diabetes medications with specific controlled dose titration and monitoring with a proper assessment of the response to the medication and any side effects over a span of 6 months. The main focus of this study was to use the two groups to determine any major changes to HbA1C levels.

The Response to Oral Agents in Diabetes study was created to bring forth attention towards the narrow angle of observational data in a prospective study of those using specific oral diabetes medications.  The first six months were designated to create a protocol that focused on dose titration, monitoring if patients were adherent to their medications, side effects of the medications, and any other responses received for the adverse effects of the medication. The ROAD study had implemented a long-term community follow up that would last up to at least 10 years. This study is a very good example of strong prospective study data that researchers can use to create better-targeted therapies for patients with diabetes. The primary outcome measure for this study was the change in HbA1C levels in a time frame of six months. This particular study had 29 participants who were placed on three different comparators: Gliclazide MR 30 mg daily and increased to 60 mg if HbA1C was greater than 7 percent at 3 months, Sitagliptin 100 mg daily for 6 months or Pioglitazone 30 mg daily and increased to 45 mg daily if HbA1c was greater than 7 percent at 3 months. If a patient were drug naïve they would be placed on metformin 500 mg once daily for 1 week for a total of 6 months of treatment.

A bit of background information on Glicazide MR 30 mg: it is a sulfonylurea from class of insulin secretagogues, which act by stimulating the beta cells of the pancreas to release insulin. Sulfonylureas are famous for causing hypoglycemia, but this medication causes less hypoglycemia than other medications in its class. This medication is used when dietary changes, exercise and the use of metformin might not be enough. Glicazide when compared to metformin does not support weight loss in  non-insulin-dependent patients with obesity and diabetes to the same extent as metformin. Studies have shown that Glicazide is a good oral medication used for patients with obesity who have uncontrolled diabetes. It is a beneficial choice as a second line of therapy for patients after they use medications such as metformin to help control their blood glucose levels. 

Pioglitazone is a medication in the class of thiazolidinediones. They are used in the treatment of type 2 diabetes and they act by increasing insulin sensitivity in tissues. They stimulate the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-γ), which in turn helps modulate gene transcription that is a key part in controlling glucose and lipid metabolism in the muscle, fat, and liver tissue. There are many adverse effects associated with this medication, which is why it is usually a second line choice when it comes to oral diabetes medications. It does help to regulate HbA1C levels quite well, but when you measure the risk to benefit ratio, there is concern that it might not be the most ideal choice for some patients.

Patients were divided into two cohorts. Cohort one was a type 2 diabetes patient diagnosed more than 6 weeks prior to the first visit; these patients were placed on metformin treatment therapy. Cohort two was second line treatment given to patients who were treated with metformin for more than three months or were metformin intolerant.

In the primary outcome measure for the change in HbA1C level, 5 patients each were placed on Glicazide MR, Sitagliptin, and Pioglitazone. As for the metformin, 8 participants were analyzed from there. From the data retrieved, there was a negative 1.59 percent decrease in HbA1C levels with patients who were on metformin. Also it should be noted that there were more participants that were placed on metformin as compared to the other oral medications, which could also affect the change in HbA1C levels. From this data, we can see a correlation with metformin use and the decrease in HbA1C levels; Pioglitazone is a close second in helping reduce levels of HbA1C. This is important because we know metformin is usually well tolerated, with most side effects being related to the gastrointestinal tract.

Practice Pearls

  • Health care providers, especially those dealing with patients with diabetes, need to do proper research as to which oral medications would be best to use with their patients and why.
  • Metformin use showed a significant decrease in HbA1C levels as compared to the three second line treatment choices studied.
  • Data regarding oral diabetes medications and their effect in reducing HbA1C should be dissected for providers to understand the risk: benefit ratio associated with these medications.


References for “Which Oral Meds Are Best At Reducing HbA1c?”:

Craig J. Currie, Gerit-Holger Schernthaner. “Do We Still Need Pioglitazone for the Treatment of Type 2 Diabetes? A Risk-Benefit Critique in 2013.” Diabetes Care, American Diabetes Association, 1 Aug. 2013, https://care.diabetesjournals.org/content/36/Supplement_2/S155.

Holman, R. “Metformin as First Choice in Oral Diabetes Treatment: the UKPDS Experience.” Journees Annuelles De Diabetologie De L’Hotel-Dieu, U.S. National Library of Medicine, 2007, https://www.ncbi.nlm.nih.gov/pubmed/18613325.

Landman, Gijs W D, et al. “Safety and Efficacy of Gliclazide as Treatment for Type 2 Diabetes: a Systematic Review and Meta-Analysis of Randomized Trials.” PloS One, Public Library of Science, 12 Feb. 2014, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3922704/.

 “Response To Oral Agents in Diabetes (ROAD)- Pilot Study – Study Results.” Response To Oral Agents in Diabetes (ROAD)- Pilot Study – Study Results – ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/results/NCT00780715?recrs=e&rslt=With&cond=diabetes&draw=5&rank=63&view=results.

 Hira Gohar, Florida A&M University, College of Pharmacy, PharmD Candidate