Metformin's effectiveness in preventing prednisone-induced hyperglycemia in hematological cancers

J Oncol Pharm Pract. 2020 Jun;26(4):823-834. doi: 10.1177/1078155219873048. Epub 2019 Sep 7.

Abstract

Background: Research has established the development of steroid-induced hyperglycemia as a glucometabolic side effect of high-dose prednisone therapy. Few studies, however, have demonstrated preventative measures that could effectively curtail this side effect in susceptible patients undergoing high-dose prednisone treatment.

Objective: To assess metformin's prophylactic effectiveness of prednisone-induced hyperglycemia among hematological cancer patients.

Setting: Prospective randomized controlled trial conducted at the Kenyatta National Hospital Oncology Clinic and Wards, Nairobi, Kenya.

Method: Non-hyperglycemic hematological cancer patients on current or newly initiated high-dose prednisone-based chemotherapy were randomized to receive metformin 850 mg once then 850 mg twice daily for two successive weeks each or to the control group receiving the standard care. Patients were subjected to once weekly fasting and 2-h postprandial glucose measurements for four weeks.

Main outcome measure: The primary outcome of measure was the development of hyperglycemia defined by fasting capillary blood glucose values >5.6 mmol/L or 2-h postprandial capillary blood glucose values >7.8 mmol/L.

Results: Eighteen of 24 randomized patients completed the study (11 control and 7 treatment). The proportion of the control subjects that developed prediabetes was 72.7% (95% confidence interval 45.5-90.9%) using fasting glucose and 54.5% (95% confidence interval 27.3-81.8%) using 2-h postprandial glucose. One treatment group participant developed prediabetes using fasting glucose, representing 14.3% (95% confidence interval 0-42.9%). No prediabetes was detected using the 2-h postprandial glucose. Analysis of mean fasting glucose between the two arms found no significant difference. However, significant differences in mean 2-h postprandial glucose were noted in week 2 (p = 0.0144), week 3 (p = 0.0095), and week 4 (p = 0.0074) of the study. Double dose (1700 mg) metformin was more effective in lowering blood glucose than single dose (850 mg) (p = 1.0000 (fasting), p = 0.4531(2-h postprandial).

Conclusion: Metformin's prophylactic effectiveness was demonstrated in this randomized study on new and previously exposed non-diabetic cancer patients on high-dose prednisone-based chemotherapy.

Keywords: Cancer; hyperglycemia; metformin; prednisone; prevention.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / drug effects
  • Fasting
  • Female
  • Hematologic Neoplasms / drug therapy
  • Humans
  • Hyperglycemia / chemically induced
  • Hyperglycemia / prevention & control*
  • Hypoglycemic Agents / administration & dosage*
  • Kenya
  • Male
  • Metformin / administration & dosage*
  • Middle Aged
  • Postprandial Period
  • Prednisone / adverse effects*
  • Prednisone / therapeutic use
  • Prospective Studies
  • Young Adult

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Metformin
  • Prednisone