Thiazide Diuretic–Induced Change in Fasting Plasma Glucose: a Meta-analysis of Randomized Clinical Trials

Background/Purpose. To compare efficacy and safety of short- and long-acting GLP-1 receptor agonists (GLP-1 RAs), both used in combination with basal insulin in patients with type 2 diabetes. Data Sources/Study Selection. Randomized controlled trials comparing the co-administration of short- or long-acting GLP-1 RAs and basal insulin with basal insulin ± placebo were identified (PubMed search). Of 974 identified publications 14 clinical trials were included. Eight trials examined short-acting and six long-acting GLP-1 RAs. Data Extraction/Data Synthesis. Differences in HbA1c, fasting plasma glucose, body weight and adverse events were compared between studies using short- or long-acting GLP-1 RAs by random-effects meta-analysis. Limitations. Relatively small numbers of available publications, some heterogeneity regarding protocols and differences in the GLP-1 RA compound used. Conclusions. Long-acting GLP-1 RAs more effectively reduced HbA1c (∆ - 6 mmol/mol, [95 % CI - 10; - 2], p= 0.007), fasting plasma glucose (∆ - 0.7 mmol/l [- 1.2; - 0.3] p= 0.007) and body weight (∆ - 1.4 kg [- 2.2; - 0.6] p= 0.002) and raised the proportion of patients achieving an HbA1c target < 7.0% (< 53 mmol/mol; p= 0.03) more than the short-acting ones. Patients reporting symptomatic (p= 0.048), but not severe hypoglycemia (p= 0.96) were fewer with long- vs. short-acting GLP-1 RAs added to insulin. The proportion of patients reporting nausea (- 52 %; p < 0.0001) or vomiting (- 36 %; p= 0.0002) was lower with long-acting GLP-1 RAs. Overall, GLP-1 RAs improved HbA1c, fasting plasma glucose and body weight when added to basal insulin. However, long-acting GLP-1 RAs were significantly more effective for glycemic and body weight control and displayed better gastro-intestinal tolerability.

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Combined therapy of somatostatin analogues with pegvisomant for the treatment of acromegaly: a meta-analysis of prospective studies

10.21203/rs.2.14260/v1 ◽

2019 ◽

Author(s):

Lingyun Ma ◽

Daohuang Luo ◽

Ting Yang ◽

Songtao Wu ◽

Min Li ◽

...

Keyword(s):

Combination Therapy ◽

Plasma Glucose ◽

Fasting Plasma Glucose ◽

Plasma Insulin ◽

Combined Therapy ◽

Meta Analysis ◽

Somatostatin Analogues ◽

Glycosylated Haemoglobin ◽

Fasting Plasma ◽

Fasting Plasma Insulin

Abstract Background: Acromegaly is a rare, chronic and severe disease . Drug therapy including somatostatin analogues , dopamine receptor agonists and growth hormone receptor antagonists are commonly used to treat patients who do not responde to surgery. T he use of combination therapy with PEG and SAs has become more common over the last decade . We performed this study t o accurately evaluate the effect of combination therapy of somatostatin analogues (SAs) with pegvisomant (PEG) on acromegalic patients. Methods: PubMed, EMBASE, The Cochrane Library, and ClinicalTrials.gov were searched for relevant studies. Prospective clinical trials treating acromegaly with the co-administration of SAs and PEG were included. We performed a meta-analysis by using Stata 12.1 . Sensitivity analysis was conducted to explore heterogeneity. Results: Eight studies were included in this meta-analysis. The overall rate of serum insulin-like growth factor 1 (IGF-1) normalization was 75% (95% CI: 50%–93%; I 2 =93.60%). The combination therapy did not significantly change patients’ fasting plasma glucose (ES: 0.011 mmol*L -1 ; 95% CI: − 0.374 to 0.397 mmol*L -1 ; P=0.954) or glycosylated haemoglobin (ES: -0.106%; 95% CI: − 0.302% to 0.089%; P=0.285) while decreasing the fasting plasma insulin (ES: −21.487 pmol*L-1; 95% CI: −35.713 to -7.260 pmol*L-1; P=0.003). Elevation of liver enzyme levels was found in 14% (95% CI: 10% to 19%) of the patients. Conclusions: Combined therapy of SAs and PEG effectively normalized IGF-1 levels in most of the patients whose IGF-1 level was greater than the upper limit of normal after high dose SAs monotherapy. The combination therapy significantly decreased patients’ fasting plasma insulin. However, improved fasting plasma glucose or glycosylated haemoglobin was not found during the combination therapy. Moreover, elevated liver enzyme levels were observed in a small number of patients, which suggests a need for liver function monitoring. Trial registration We have our protocol registered in PROSPERO. (Registration number: CRD42019115549)

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