Efficacy And Safety of Canagliflozin among Patients with type 2 diabetes Mellitus: a Systematic review and meta-analysis

Abstract

OBJECTIVES: To inform a multiple technology appraisal to be conducted by the National Institute for Health and Care Excellence on the use of agents that inhibit sodium-glucose co-transporter 2 (SGLT2), canagliflozin was assessed as monotherapy treatment for T2DM. METHODS: A systematic literature review identified 36 trials, which were used to perform a Bayesian NMA to estimate the relative efficacy (HbA1c, weight, and systolic blood pressure [SBP]) of canagliflozin monotherapy at 26±4 weeks compared to dipeptidyl peptidase-4 inhibitors (DPP-4s), sulphonylurea, pioglitazone, and SGLT2 inhibitors. Networks of evidence had treatment-and dosespecific nodes for DPP-4s, pioglitazone, and SGLT2 inhibitors. Relative efficacy was evaluated based on absolute differences and Bayesian probabilities (P), where 30%< P > 70% were chosen to indicate a smaller and larger effect, respectively. RESULTS: Results presented here focus on comparisons to the most relevant anti-hyperglycaemic therapies in the UK; sitagliptin, gliclazide, pioglitazone, dapagliflozin 10mg, and empagliflozin 10mg/25mg. Canagliflozin 300mg was associated with greater reductions in HbA1c (Δ -0.29 to -0.52) versus all comparators. Canagliflozin 100mg conferred reductions in HbA1c at least as large as other comparator (Δ -0.03 to -0.26). Canagliflozin was associated with larger reductions in weight (kg) versus all comparators (Δ -0.41 to -7.03), except for canagliflozin 100mg versus empagliflozin 25mg, where the reduction was similar (Δ -0.19). Canagliflozin 300mg was associated with larger reductions in SBP (Δ -1.06 to -6.29) versus all comparators. Canagliflozin 100mg was associated with greater reductions in SBP versus empagliflozin 10mg, pioglitazone, and sitagliptin (Δ -1.11 to -4.60) and provided comparable reductions in SBP versus dapagliflozin 10mg and empagliflozin 25mg (Δ 0.65 and -0.31). CONCLUSIONS: The results of this NMA suggest that canagliflozin 300mg monotherapy was associated with consistently greater HbA1c and SBP reductions versus all comparators, relevant to UK prescribing habits; while canagliflozin 100mg was at least similar. Weight reductions were larger for both doses of canagliflozin compared to all comparators.

Adverse events associated with sodium glucose co-transporter 2 inhibitors: an overview of quantitative systematic reviews

“…We identified 1289 unique citations, of which 47 quantitative systematic reviews met our inclusion criteria (Figure 1 and Table 1). Twenty-two reviews (47%) reported no funding sou rce, [17][18][19][20][21][22][23][24]27,28,[30][31][32]35,38,39,43,44,50,52,53,55 while nine reviews (19%) received funding from government, 25,26,29,37,40,41,51,54,59 five reviews (11%) received internal funding, [45][46][47][48][49] three reviews (6%) received foundational funding 16,34,36 and one review (2%) was funded by private industry. 57 A funding source was not disclosed in seven reviews (15%).…”

“…44 Twentyfour (52%) reviews were considered critically low quality, [16][17][18][20][21][22][23][24][27][28][29]32,34,[38][39][40]43,45,50,51,54,55,59,62 11 (23%) reviews were considered low quality 19,33,46,[47][48][49]52,56,57,60,61 and 11 (23%) reviews were considered moderate quality. 25,26,30,31,[35][36][37]41,42,53,55 From the 47 included reviews, there were 958 point estimates reporting on 59 unique adverse effects. The most frequently reported estimates (n = 213, 22%) were for urinary tract infection (Figure 3).…”