Benefits and harms of drug treatment for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials.

OBJECTIVE: To compare the benefits and harms of drug treatments for adults with type 2 diabetes, adding non-steroidal mineralocorticoid receptor antagonists (including finerenone) and tirzepatide (a dual glucose dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist) to previously existing treatment options. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Ovid Medline, Embase, and Cochrane Central up to 14 October 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Eligible randomised controlled trials compared drugs of interest in adults with type 2 diabetes. Eligible trials had a follow-up of 24 weeks or longer. Trials systematically comparing combinations of more than one drug treatment class with no drug, subgroup analyses of randomised controlled trials, and non-English language studies were deemed ineligible. Certainty of evidence was assessed following the GRADE (grading of recommendations, assessment, development and evaluation) approach. RESULTS: The analysis identified 816 trials with 471 038 patients, together evaluating 13 different drug classes; all subsequent estimates refer to the comparison with standard treatments. Sodium glucose cotransporter-2 (SGLT-2) inhibitors (odds ratio 0.88, 95% confidence interval 0.83 to 0.94; high certainty) and GLP-1 receptor agonists (0.88, 0.82 to 0.93; high certainty) reduce all cause death; non-steroidal mineralocorticoid receptor antagonists, so far tested only with finerenone in patients with chronic kidney disease, probably reduce mortality (0.89, 0.79 to 1.00; moderate certainty); other drugs may not. The study confirmed the benefits of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing cardiovascular death, non-fatal myocardial infarction, admission to hospital for heart failure, and end stage kidney disease. Finerenone probably reduces admissions to hospital for heart failure and end stage kidney disease, and possibly cardiovascular death. Only GLP-1 receptor agonists reduce non-fatal stroke; SGLT-2 inhibitors are superior to other drugs in reducing end stage kidney disease. GLP-1 receptor agonists and probably SGLT-2 inhibitors and tirzepatide improve quality of life. Reported harms were largely specific to drug class (eg, genital infections with SGLT-2 inhibitors, severe gastrointestinal adverse events with tirzepatide and GLP-1 receptor agonists, hyperkalaemia leading to admission to hospital with finerenone). Tirzepatide probably results in the largest reduction in body weight (mean difference -8.57 kg; moderate certainty). Basal insulin (mean difference 2.15 kg; moderate certainty) and thiazolidinediones (mean difference 2.81 kg; moderate certainty) probably result in the largest increases in body weight. Absolute benefits of SGLT-2 inhibitors, GLP-1 receptor agonists, and finerenone vary in people with type 2 diabetes, depending on baseline risks for cardiovascular and kidney outcomes (https://matchit.magicevidence.org/230125dist-diabetes). CONCLUSIONS: This network meta-analysis extends knowledge beyond confirming the substantial benefits with the use of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing adverse cardiovascular and kidney outcomes and death by adding information on finerenone and tirzepatide. These findings highlight the need for continuous assessment of scientific progress to introduce cutting edge updates in clinical practice guidelines for people with type 2 diabetes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022325948.

High Interest in Long-acting Injectable Pre-exposure Prophylaxis (LAI-PrEP) for HIV Prevention Among Men Who Have Sex With Men (MSM): Result From A Nationwide Survey in Malaysia.

The recent approval of long-acting injectable cabotegravir (CAB-LA) as PrEP for HIV prevention could be an attractive alternative for MSM, particularly among those who face barriers to adherence using the oral pill. This study reports on the awareness of long-acting injectable PrEP (LAI-PrEP) and factors associated with interest in LAI-PrEP use among a nationwide sample of MSM in Malaysia. An online cross-sectional survey was conducted between August and September 2021 to explore perspectives on PrEP modalities among Malaysian MSM (N = 870). Convenience sampling was used to recruit participants using ads on two platforms hornet and facebook. While only 9.1% of the study participants were aware of LAI-PrEP, the majority had heard of oral PrEP (80.9%). After giving a description of it, a large majority (86.6%) expressed interest in using it if made accessible. Those who had a prior history of HIV testing (aOR = 1.9; 95% CI = 1.2-3.2) were more likely to use LAI-PrEP. Interestingly, despite the concerns related to potential high cost (aOR = 3.4; 95% CI = 2.1-5.5) and long-term side effects (aOR = 1.9; 95% CI = 1.2-3.1), the majority of the participants were interested in using LAI-PrEP. Those who were afraid of (or disliked) syringes were less interested in using it (aOR = 0.2; 95% CI; 0.1-0.4). In the recent context that LAI-PrEP was shown to be safe and effective at preventing HIV, our results indicate its potential relevance as an additional PrEP option that could accelerate the uptake and scale-up of PrEP. However, it is crucial to conduct future research urgently to improve the understanding of strategies that could enhance the accessibility, acceptability, and affordability of LAI-PrEP for MSM in low- and middle-income countries, including Malaysia.

Clinic-Integrated Smartphone App (JomPrEP) to Improve Uptake of HIV Testing and Pre-exposure Prophylaxis Among Men Who Have Sex With Men in Malaysia: Mixed Methods Evaluation of Usability and Acceptability.

BACKGROUND: HIV disproportionately affects men who have sex with men (MSM). In Malaysia, where stigma and discrimination toward MSM are high, including in health care settings, mobile health (mHealth) platforms have the potential to open new frontiers in HIV prevention. OBJECTIVE: We developed an innovative, clinic-integrated smartphone app called JomPrEP, which provides a virtual platform for Malaysian MSM to engage in HIV prevention services. In collaboration with the local clinics in Malaysia, JomPrEP offers a range of HIV prevention (ie, HIV testing and pre-exposure prophylaxis [PrEP]) and other support services (eg, referral to mental health support) without having to interface face to face with clinicians. This study evaluated the usability and acceptability of JomPrEP to deliver HIV prevention services for MSM in Malaysia. METHODS: In total, 50 PrEP-naive MSM without HIV in Greater Kuala Lumpur, Malaysia, were recruited between March and April 2022. Participants used JomPrEP for a month and completed a postuse survey. The usability of the app and its features were assessed using self-report and objective measures (eg, app analytics, clinic dashboard). Acceptability was evaluated using the System Usability Scale (SUS). RESULTS: The participants' mean age was 27.9 (SD 5.3) years. Participants used JomPrEP for an average of 8 (SD 5.0) times during 30 days of testing, with each session lasting an average of 28 (SD 38.9) minutes. Of the 50 participants, 42 (84%) ordered an HIV self-testing (HIVST) kit using the app, of whom 18 (42%) ordered an HIVST more than once. Almost all participants (46/50, 92%) initiated PrEP using the app (same-day PrEP initiation: 30/46, 65%); of these, 16/46 (35%) participants chose PrEP e-consultation via the app (vs in-person consultation). Regarding PrEP dispensing, 18/46 (39%) participants chose to receive their PrEP via mail delivery (vs pharmacy pickup). The app was rated as having high acceptability with a mean score of 73.8 (SD 10.1) on the SUS. CONCLUSIONS: JomPrEP was found to be a highly feasible and acceptable tool for MSM in Malaysia to access HIV prevention services quickly and conveniently. A broader, randomized controlled trial is warranted to evaluate its efficacy on HIV prevention outcomes among MSM in Malaysia. TRIAL REGISTRATION: ClinicalTrials.gov NCT05052411; https://clinicaltrials.gov/ct2/show/NCT05052411. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/43318.