METHODS: We reviewed a cohort of people with T2D seeking care from two tertiary hospitals in the metropolitan cities of the state of Selangor and Negeri Sembilan from January 2012 to May 2021. To identify the 3-year predictor of developing CKD (primary outcome) and CKD progression (secondary outcome), the dataset was randomly split into a training and test set. A Cox proportional hazards (CoxPH) model was developed to identify predictors of developing CKD. The resultant CoxPH model was compared with other machine learning models on their performance using C-statistic.
RESULTS: The cohorts included 1992 participants, of which 295 had developed CKD and 442 reported worsening of kidney function. Equation for the 3-year risk of developing CKD included gender, haemoglobin A1c, triglyceride and serum creatinine levels, estimated glomerular filtration rate, history of cardiovascular disease and diabetes duration. For risk of CKD progression, the model included systolic blood pressure, retinopathy and proteinuria. The CoxPH model was better at prediction compared with other machine learning models examined for incident CKD (C-statistic: training 0.826; test 0.874) and CKD progression (C-statistic: training 0.611; test 0.655). The risk calculator can be found at https://rs59.shinyapps.io/071221/.
CONCLUSIONS: The Cox regression model was the best performing model to predict people with T2D who will develop a 3-year risk of incident CKD and CKD progression in a Malaysian cohort.
METHODS: MEDLINE, EMBASE and CENTRAL were searched from inception to 13 July 2021 for randomised controlled trials comparing second-line glucose lowering therapies with placebo, standard care or one another. Primary outcomes included cardiovascular and renal outcomes. Secondary outcomes were non-cardiovascular adverse events. Risk ratios (RRs) and corresponding confidence intervals (CI) or credible intervals (CrI) were reported within pairwise and network meta-analysis. The quality of evidence was evaluated using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) criteria. Number needed to treat (NNT) and number needed (NNH) to harm were calculated at 5 years using incidence rates and RRs. PROSPERO (CRD42020168322).
RESULTS: We included 38 trials from seven classes of glucose-lowering therapies. Both sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP1RA) showed moderate to high certainty in reducing risk of 3-point major adverse cardiovascular events, 3P-MACE (network estimates: SGLT2i [RR 0.90; 95% CrI 0.84-0.96; NNT, 59], GLP1RA [RR 0.88; 95% CrI 0.83-0.93; NNT, 50]), cardiovascular death, all-cause mortality, renal composite outcome and macroalbuminuria. SGLT2i also showed high certainty in reducing risk of hospitalization for heart failure (hHF), ESRD, acute kidney injury, doubling in serum creatinine and decline in eGFR. GLP1RA were associated with lower risk of stroke (high certainty) while glitazone use was associated with an increased risk of hHF (very low certainty). The risk of developing ESRD was lower with the use of sulphonylureas (low certainty). For adverse events, sulphonylureas and insulin were associated with increased hypoglycaemic events (very low to low certainty), while GLP1RA increased the risk of gastrointestinal side effects leading to treatment discontinuation (low certainty). DPP-4i increased risk of acute pancreatitis (low certainty). SGLT2i were associated with increased risk of genital infection, volume depletion (high certainty), amputation and ketoacidosis (moderate certainty). Risk of fracture was increased with the use of glitazones (moderate certainty).
CONCLUSIONS: SGLT2i and GLP1RA were associated with lower risk for different cardiorenal end points, when used as an adjunct to metformin in people with type 2 diabetes. Additionally, SGLT2i demonstrated benefits in reducing risk for surrogate end points in kidney disease progression. Safety outcomes differ among the available pharmacotherapies.
METHODS: A state-transition microsimulation model was developed to compare the clinical and economic outcomes of 4 treatments: standard care, dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter-2 inhibitors (SGLT2is), and glucagon-like peptide-1 receptor agonists. Cost-effectiveness was assessed from a healthcare provider's perspective over a lifetime horizon with 3% discount rate in a hypothetical cohort of people with T2D. Data input were informed from literature and local data when available. Outcome measures include costs, quality-adjusted life-years, incremental cost-effectiveness ratios, and net monetary benefits. Univariate and probabilistic sensitivity analyses were performed to assess uncertainties.
RESULTS: Over a lifetime horizon, the costs to treat a person with T2D ranged from RM 12 494 to RM 41 250, whereas the QALYs gains ranged from 6.155 to 6.731, depending on the treatment. Based upon a willingness-to-pay threshold of RM 29 080 per QALY, we identified SGLT2i as the most cost-effective glucose-lowering treatment, as add-on to standard care over patient's lifetime, with the net monetary benefit of RM 176 173 and incremental cost-effectiveness ratios of RM 12 279 per QALY gained. The intervention also added 0.577 QALYs and 0.809 LYs compared with standard care. Cost-effectiveness acceptability curve showed that SGLT2i had the highest probability of being cost-effective in Malaysia across varying willingness-to-pay threshold. The results were robust to various sensitivity analyses.
CONCLUSIONS: SGLT2i was found to be the most cost-effective intervention to mitigate diabetes-related complications.
PATIENTS AND METHODS: A prospective observational cohort study was conducted on 86 patients with T2DM who had been receiving metformin monotherapy for <1 year. Patients showing ≥0.5% reduction in HbA1c levels from baseline within 3 months and remained low for at least another 3 months were defined as responders while those patients with <0.5% reduction in HbA1c levels and/or those whom started a new class of glucose-lowering drug(s) because of unsatisfactory reduction were defined as non-responders. In addition, good glycemic control was observed when HbA1c ≤7.0%, and the above values were regarded as poor. Genotyping of rs72552763 SNP was performed using TaqMan® Drug Metabolism Enzyme Genotyping Assay and its association with metformin response and glycemic control were assessed by measuring the change in HbA1c and fasting blood glucose levels using Chi-square, logistic regression and Mann-Whitney U-test. Statistical significance was set at p <0.05.
RESULTS: The minor allele frequency of the rs72552763 SNP of SLC22A1 was 9.3%. Metformin response was significantly higher in deletion_GAT (del_G) genotypes as compared to the wild-type GAT_GAT (G_G) genotypes. Furthermore, a significantly lower median treatment HbA1 level was found in del_G genotypes as compared to G_G genotypes. However, the association of rs72552763 with metformin response was not replicated at the allele level. In contrast, the minor del_allele was significantly associated with good glycemic control compared to the G_allele, though not replicated at del_G genotypes level.
CONCLUSION: This study demonstrated that metformin response was significantly higher in study participants with a heterozygous carrier of M420del variants of SLC22A1 as compared to the wild-type G_G genotypes after 3 months of treatment.
OBJECTIVE: This study aimed to evaluate the effects of a patient-centered CST program on patient-centered communication scores, communication self-efficacy, and attitudes toward concordance among pharmacists in public hospitals.
METHODS: A communication skills training (CST) program was conducted among hospital pharmacists. This training intervention was developed based on patient-centered communication frameworks and techniques, namely the Four Habits Model and motivational interviewing. A pre-test/post-test quasi-experimental design was implemented for the evaluation. Pharmacists underwent pre-test/post-test audiotaped simulated consultations and completed questionnaires, including the Revised United States-Leeds Attitudes Toward Concordance scale (RUS-LATCon) and Communication Self-Efficacy scale. The Four Habits Coding Scheme (FHCS) was used to evaluate patient-centered communication scores from the audiotapes, and the Wilcoxon signed-rank test was used to analyze for differences in the pre- and post-intervention scores.
RESULTS: A total of 38 pharmacists from four tertiary hospitals participated in this study and completed the pre-test. However, due to the impact of COVID-19, only 23 pharmacists completed the post-test data collection. Improvements were noted in the FHCS scores post-training, including items related to exploring patients' concerns, acceptability, and barriers to treatment. Based on the questionnaire, there was an improvement in recognizing patients' needs and potential medication uncertainty and an increase in the overall communication self-efficacy scores after the training.
CONCLUSIONS: CST may help improve the adoption of patient-centered communication in pharmacists' consultations with patients.
PATIENTS AND METHODS: A retrospective observational study was conducted on 47 T2DM patients on metformin treatment for <3 years to assess the association of SLC22A1 (rs72552763) polymorphism with metformin induced gastrointestinal intolerance. Accordingly, 24 metformin tolerant and 23 metformin intolerant individuals with T2DM were recruited. Genotyping of rs72552763 was performed using TaqMan® Drug Metabolism Enzyme Genotyping Assay and its association to metformin induced gastrointestinal intolerance was assessed based on switching to a new class of glucose lowering agents or failure to up titrate dose due to metformin induced gastrointestinal intolerance. Chi-square, logistic regression and Mann-Whitney statistical tests were used as appropriate. Statistical significance was set at p < 0.05.
RESULTS: In our study, no significant association was observed between rs72552763 and metformin induced gastrointestinal intolerance. We found that the female gender and physical inactivity were risk factors for metformin gastrointestinal intolerance.
CONCLUSION: Our study found that the Met420del variant of SLC22A1 (rs72552763) was not associated with metformin induced gastrointestinal intolerance in Ethiopian patients with T2DM. This is the study first to investigate the association of rs72552763 with metformin intolerance in the Ethiopian population with T2DM. However, the findings need to be cautiously interpreted given the relatively small sample size. In addition, a more complete investigation of SLC22A1 variants would be required to fully assess the effect of the gene on metformin induced gastrointestinal intolerance as several variants with a more severe loss of function have been described.