Zhou · Pituitary 2021 · systematic review and meta-analysis · n=33 studies

Effect of long-term growth hormone replacement on glucose metabolism in adults with growth hormone deficiency: a systematic review and meta-analysis.

Level 1 - systematic review of randomized trials

Systematic review and meta-analysis of randomized controlled trials and prospective open-label studies

PubMed 32888174 · doi:10.1007/s11102-020-01079-3 · record verified 2026-08-26

What was done

Authors searched MEDLINE, EMBASE, and the Cochrane Library through March 2020 for studies evaluating the effect of growth hormone replacement therapy on glucose metabolism in adults with growth hormone deficiency. The meta-analysis included 33 studies (11 randomized controlled trials and 22 prospective open-label studies) stratified by follow-up duration: 6 to 12 months versus more than 12 months.

What was found

At 6 to 12 months, growth hormone therapy significantly increased fasting plasma glucose (SMD 0.37; 95% CI 0.25 to 0.49; I2 = 0%; P < 0.00001), fasting insulin (SMD 0.20; 95% CI 0.08 to 0.33; I2 = 9%; P = 0.001), HbA1c (SMD 0.31; 95% CI 0.17 to 0.46; I2 = 10%; P < 0.0001), and HOMA-IR (SMD 0.28; 95% CI 0.08 to 0.47; I2 = 13%; P = 0.006). At more than 12 months, there were no significant changes in fasting insulin (SMD 0.14; 95% CI -0.09 to 0.37; I2 = 0%; P = 0.24), HbA1c (SMD -0.02; 95% CI -0.30 to 0.26; I2 = 72%; P = 0.89), or HOMA-IR (SMD 0.04; 95% CI -0.24 to 0.31; I2 = 0%; P = 0.80), but fasting plasma glucose remained significantly elevated (SMD 0.41; 95% CI 0.29 to 0.53; I2 = 0%; P < 0.00001).

Why it matters

This review indicates that worsening of insulin resistance and glycated hemoglobin during growth hormone replacement is transient, though fasting glucose elevations persist over longer treatment durations.

Limits

Twenty-two of the 33 included studies were non-randomized prospective open-label studies. Total participant count is not provided in the abstract. HbA1c at more than 12 months had substantial heterogeneity (I2 = 72%). Growth hormone dosing strategies, baseline patient metabolic status, and incident diabetes rates were not reported in the abstract.