Efficacy and safety of fixed‐dose combination therapy with gemigliptin (50 mg) and rosuvastatin compared with monotherapy in patients with type 2 diabetes and dyslipidaemia (BALANCE): A multicentre, randomized, double‐blind, controlled, phase 3 trial

Bae, Ji Cheol; Min, Kyung Up; Kim, Yong Hyun; Kim, Kyoung Ah; Hong, Eun‐Gyoung; Park, Cheol‐Young; Han, Song Yi; Soo, Bong

doi:10.1111/dom.13491

“…After removing duplicates, 62 eligible studies were identified by screening of the title and abstract and assessing the full text (fig 1). 30315051525354555657585960616263646566676869707172737475767778798081828384858687888990919293949596979899100101102103104105106107108109 Supplementary table 3 provides a list of studies excluded after assessing the full text, with reasons for exclusion.…”

Section: Resultsmentioning

confidence: 99%

Associations between statins and adverse events in primary prevention of cardiovascular disease: systematic review with pairwise, network, and dose-response meta-analyses

Cai

¹

,

Abel

²

,

Langford

³

et al. 2021

BMJ

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Objective To assess the associations between statins and adverse events in primary prevention of cardiovascular disease and to examine how the associations vary by type and dosage of statins. Design Systematic review and meta-analysis. Data sources Studies were identified from previous systematic reviews and searched in Medline, Embase, and the Cochrane Central Register of Controlled Trials, up to August 2020. Review methods Randomised controlled trials in adults without a history of cardiovascular disease that compared statins with non-statin controls or compared different types or dosages of statins were included. Main outcome measures Primary outcomes were common adverse events: self-reported muscle symptoms, clinically confirmed muscle disorders, liver dysfunction, renal insufficiency, diabetes, and eye conditions. Secondary outcomes included myocardial infarction, stroke, and death from cardiovascular disease as measures of efficacy. Data synthesis A pairwise meta-analysis was conducted to calculate odds ratios and 95% confidence intervals for each outcome between statins and non-statin controls, and the absolute risk difference in the number of events per 10 000 patients treated for a year was estimated. A network meta-analysis was performed to compare the adverse effects of different types of statins. An E max model based meta-analysis was used to examine the dose-response relationships of the adverse effects of each statin. Results 62 trials were included, with 120 456 participants followed up for an average of 3.9 years. Statins were associated with an increased risk of self-reported muscle symptoms (21 trials, odds ratio 1.06 (95% confidence interval 1.01 to 1.13); absolute risk difference 15 (95% confidence interval 1 to 29)), liver dysfunction (21 trials, odds ratio 1.33 (1.12 to 1.58); absolute risk difference 8 (3 to 14)), renal insufficiency (eight trials, odds ratio 1.14 (1.01 to 1.28); absolute risk difference 12 (1 to 24)), and eye conditions (six trials, odds ratio 1.23 (1.04 to 1.47); absolute risk difference 14 (2 to 29)) but were not associated with clinically confirmed muscle disorders or diabetes. The increased risks did not outweigh the reduction in the risk of major cardiovascular events. Atorvastatin, lovastatin, and rosuvastatin were individually associated with some adverse events, but few significant differences were found between types of statins. An E max dose-response relationship was identified for the effect of atorvastatin on liver dysfunction, but the dose-response relationships for the other statins and adverse effects were inconclusive. Conclusions For primary prevention of cardiovascular disease, the risk of adverse events attributable to statins was low and did not outweigh their efficacy in preventing cardiovascular disease, suggesting that the benefit-to-harm balance of statins is generally favourable. Evidence to support tailoring the type or dosage of statins to account for safety concerns before starting treatment was limited. Systematic review registration PROSPERO CRD42020169955.

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“…There are also FDCs containing lipid-lowering medicines and oral antihyperglycemic agents (AHAs) to try and improve outcomes in patients with both dyslipidemia and T2DM through reducing the pill burden [194]. However, currently, no FDCs containing a statin and AHA are listed in the WHO EML [111].…”

Section: Cardiovascular Diseases (Cvd)mentioning

confidence: 99%

Fixed dose drug combinations – are they pharmacoeconomically sound? Findings and implications especially for lower- and middle-income countries

Godman

¹

,

McCabe

²

,

Leong

³

2020

Expert Review of Pharmacoeconomics & Outcomes Research

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Introduction: There are positive aspects regarding the prescribing of fixed dose combinations (FDCs) versus prescribing the medicines separately. However, these have to be balanced against concerns including increased costs and their irrationality in some cases. Consequently, there is a need to review their value among lower-and middle-income countries (LMICs) which have the greatest prevalence of both infectious and noninfectious diseases and issues of affordability. Areas covered: Review of potential advantages, disadvantages, cost-effectiveness, and availability of FDCs in high priority disease areas in LMICs and possible initiatives to enhance the prescribing of valued FDCs and limit their use where there are concerns with their value. Expert commentary: FDCs are valued across LMICs. Advantages include potentially improved response rates, reduced adverse reactions, increased adherence rates, and reduced costs. Concerns include increased chances of drug:drug interactions, reduced effectiveness, potential for imprecise diagnoses and higher unjustified prices. Overall certain FDCs including those for malaria, tuberculosis, and hypertension are valued and listed in the country's essential medicine lists, with initiatives needed to enhance their prescribing where currently low prescribing rates. Proposed initiatives include robust clinical and economic data to address the current paucity of pharmacoeconomic data. Irrational FDCs persists in some countries which are being addressed.

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“…1). Ten RCTs in people with T2DM that fulfilled all the inclusion criteria were analysed in this meta-analysis [11][12][13][14][15][16][17][18][19][20]. Thirteen studies were excluded as they either evaluated the pharmacokinetic and pharmacodynamic properties of gemigliptin, did not have a valid control group, or were observational extensions of RCTs.…”

Section: Resultsmentioning

confidence: 99%

“…[17], Yang et al [18], and Yoon et al [19], which had placebos in the control arm, and the study by Bae et al [20], which had an anti-lipid medication (rosuvastatin 20 mg/day) in the control arm.…”

Section: Resultsmentioning

confidence: 99%

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Efficacy and Safety of the Novel Dipeptidyl Peptidase-4 Inhibitor Gemigliptin in the Management of Type 2 Diabetes: A Meta-Analysis

Dutta

¹

,

Agarwal

²

,

Maisnam

³

et al. 2021

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Background No meta-analysis has holistically analysed and summarised the efficacy and safety of gemigliptin in type 2 diabetes. The meta-analysis addresses this knowledge gap. Methods Electronic databases were searched for randomised controlled trials (RCTs) involving diabetes patients receiving gemigliptin in the intervention arm and placebo/active comparator in the control arm. The primary outcome was change in haemoglobin A1c (HbA1c). The secondary outcomes were alterations in glucose, glycaemic targets, lipids, insulin resistance, and adverse events. Results Data from 10 RCTs involving 1,792 patients were analysed. Four had an active control group (ACG), with metformin/dapagliflozin/sitagliptin/glimepiride as the active comparator; six had a passive control group (PCG), with placebo/rosuvastatin as controls. HbA1c reduction by gemigliptin at 24 weeks was comparable to ACG (mean difference [MD], 0.09%; 95% confidence interval [CI], −0.06 to 0.23; P =0.24; I 2 =0%; moderate certainty of evidence [MCE]), but superior to PCG (MD, −0.91%; 95% CI, −1.18 to −0.63); P <0.01; I 2 =89%; high certainty of evidence [HCE]). Gemigliptin was superior to PCG regarding achieving HbA1c <7% (12 weeks: odds ratio [OR], 5.91; 95% CI, 1.34 to 26.08; P =0.02; I 2 =74%; 24 weeks: OR, 4.48; 95% CI, 2.09 to 9.60; P <0.01; I 2 =69%; HCE). Gemigliptin was comparable to ACG regarding achieving HbA1c <7% after 24 weeks (OR, 0.92; 95% CI, 0.52 to 1.63; P =0.77; I 2 =66%; MCE). Adverse events were similar between the gemigliptin and control groups (risk ratio [RR], 1.06; 95% CI, 0.82 to 1.36; P =0.66; I 2 =35%; HCE). The gemigliptin group did not have increased hypoglycaemia (RR, 1.19; 95% CI, 0.62 to 2.28; P =0.61; I 2 =19%; HCE). Conclusion Gemigliptin has good glycaemic efficacy and is well-tolerated over 6 months of use.

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Efficacy and safety of fixed‐dose combination therapy with gemigliptin (50 mg) and rosuvastatin compared with monotherapy in patients with type 2 diabetes and dyslipidaemia (BALANCE): A multicentre, randomized, double‐blind, controlled, phase 3 trial

Abstract: The FDC of gemigliptin and rosuvastatin is safe and is effective in reducing both blood glucose and LDL-C levels; thus, it could be a good therapeutic choice for type 2 diabetic patients with dyslipidaemia.

Cited by 9 publications

References 25 publications

Associations between statins and adverse events in primary prevention of cardiovascular disease: systematic review with pairwise, network, and dose-response meta-analyses

Associations between statins and adverse events in primary prevention of cardiovascular disease: systematic review with pairwise, network, and dose-response meta-analyses

Fixed dose drug combinations – are they pharmacoeconomically sound? Findings and implications especially for lower- and middle-income countries

Efficacy and Safety of the Novel Dipeptidyl Peptidase-4 Inhibitor Gemigliptin in the Management of Type 2 Diabetes: A Meta-Analysis

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