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The placebo response of injectable GLP‐1 receptor agonists vs . oral DPP‐4 inhibitors and SGLT‐2 inhibitors: a systematic review and meta‐analysis
Author(s) -
Wit Helena M.,
Groen Maarten,
Rovers Maroeska M.,
Tack Cees J.
Publication year - 2016
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.12925
Subject(s) - placebo , medicine , adverse effect , pharmacology , gastroenterology , pathology , alternative medicine
Aims The size of the placebo response in type 2 diabetes (T2DM) treatment and its relation to the route of drug administration have not been systematically reviewed. We aimed to determine weight loss, change in HbA1c and incidence of adverse events after treatment with injectable placebo GLP‐1 receptor agonist (GLP‐1ra), compared with oral placebo DPP‐4 inhibitor (DPP‐4i) and placebo SGLT‐2 inhibitor (SGLT‐2i). Methods PubMed, EMBASE and Central were searched up to September 2014 for randomized placebo controlled trials investigating GLP‐1ra, DPP‐4i or SGLT2‐i. Data on placebo groups were extracted and pooled using a generic inverse variance random effects model. Results Sixty‐seven trials were included, involving 2522, 5290 and 2028 patients randomized to placebo GLP‐1ra, placebo DPP‐4i and placebo SGLT‐2i, respectively. Body weight decreased by −0.67 kg (95% CI −1.03, −0.31) after treatment with placebo GLP‐1ra (−0.76 kg [95% CI −1.10, −0.43] with placebo short acting GLP‐1ra and −0.32 kg [95% CI −1.75, 1.10] with placebo long acting GLP‐1ra) and by −0.31 kg (95% CI −0.64, 0.01) with placebo DPP‐4i ( P = 0.06 for difference with placebo short acting GLP‐1ra). Placebo SGLT‐2i resulted in an intermediate −0.48 kg (95% CI −0.81, −0.15) weight loss. Weight loss with placebo showed a strong correlation with the active comparator drug ( r 2 = 0.40–0.78). HbA1c changed little with placebo treatment (−0.23%, 0.10% and −0.13% for placebo GLP‐1ra, DPP‐4i and SGLT‐2i). Adverse events occurred frequently with placebo, were often similar to the active comparator drug and led to drop‐out in 2.0–2.7% of cases. Conclusions The response to placebo treatment was related to its active comparator, with injectable placebo GLP‐1ra showing a relevant response on weight, whereas oral placebo DPP4i showed no significant response. These findings may suggest that subjective expectations influence T2DM treatment efficacy, which can possibly be employed therapeutically.