J Korean Diabetes.  2019 Jun;20(2):117-126. 10.4093/jkd.2019.20.2.117.

Therapeutic Effect of Quadruple Oral Hypoglycemic Agents in Patients with Type 2 Diabetes Mellitus Who Have Insulin Limitations

• Yoo WS
• Kim DH
• Kim HJ
• Chung HK

• KMID: 2451842
• DOI: http://doi.org/10.4093/jkd.2019.20.2.117

Abstract

BACKGROUND
Insulin therapy is the treatment of choice in type 2 diabetes mellitus (T2DM) patients who are not achieving glycemic goals despite triple oral hypoglycemic agent (OHA) combination therapy. However, there is still no additional treatment option for patients who cannot afford insulin therapy or who have various clinical limitations. The purpose of this study was to evaluate the clinical efficacy and safety of four OHA combination therapy in poorly controlled T2DM patients who could not afford insulin therapy.
METHODS
Forty-seven T2DM patients were enrolled according to the following criteria: 1) glycosylated hemoglobin [HbA1c] > 8.5%, 2) ongoing treatment with 3 OHA combination therapy (metformin, sulfonylurea, dipeptidyl peptidase-4 inhibitor), or 3) combined limitations for applying insulin therapy. Patients were given the fourth OHA (pioglitazone) in addition to their previous treatment for 12 months. We evaluated changes in HbA1c, body weight, hypoglycemic events, and side effects.
RESULTS
At study completion, mean HbA1c and fasting plasma glucose were significantly reduced from 9.6% to 8.04% and from 198.4 mg/dL to 161.5 mg/dL, respectively (P < 0.001). Mean body weight was significantly increased from 66.7 kg to 69.3 kg. Hypoglycemia and side effects were observed 18 times and only 3 cases showed abnormal liver function tests or edema. In addition, subjects with higher initial HbA1c levels and HOMA-beta showed an independent association with a greater reduction in HbA1c.
CONCLUSION
The 4 OHA combination therapy is effective and safe when insulin is not feasible.

Keyword

Diabetes mellitus; type 2; Drug therapy; combination; Hypoglycemic agents

MeSH Terms

Blood Glucose
Body Weight
Diabetes Mellitus
Diabetes Mellitus, Type 2*
Drug Therapy
Edema
Fasting
Hemoglobin A, Glycosylated
Humans
Hypoglycemia
Hypoglycemic Agents*
Insulin*
Liver Function Tests
Treatment Outcome
Hypoglycemic Agents
Insulin

Figure

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  Fig. 1 Change in mean glycosylated hemoglobin (HbA1c) in patients with 4 oral hypoglycemic agent (OHA) therapy. aMean HbA1c was significantly decreased after 4 OHA therapy (P < 0.01).

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  Fig. 2 Change in mean fasting plasma glucose in patients with 4 oral hypoglycemic agent therapy. aMean fasting plasma glucose was significantly decreased after 4 OHA therapy (P < 0.01).

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  Fig. 3 Change of mean body weight in patients with 4 oral hypoglycemic agent therapy. aMean body weight was significantly increased after 4 OHA therapy (P < 0.01).

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