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Pancreatic gene variants potentially associated with dipeptidyl peptidase-4 inhibitor treatment response in Type 2 diabetes

Jamaluddin JL, Huri HZ, Vethakkan SR, Mustafa N

Pharmacogenomics, 2014 Feb;15(2):235-49.
PMID: 24444412 DOI: 10.2217/pgs.13.234

In the adult pancreas, the expression of the genes PAX4, KCNQ1, TCF7L2, KCNJ11, ABCC8, MTNR1B and WFS1 are mainly restricted to β cells to maintain glucose homeostasis. We have identified these genes as the main regulators of incretin-mediated actions, and therefore they may potentially influence the response of DPP-4 inhibitors. This review represents the first detailed exploration of pancreatic β-cell genes and their variant mechanisms, which could potentially affect the response of DPP-4 inhibitors in Type 2 diabetes. We have focused on the signaling pathways of these genes to understand their roles in gastrointestinal incretin-mediated effects; and finally, we sought to associate gene mechanisms with their Type 2 diabetes risk variants to predict the responses of DPP-4 inhibitors for this disease.

Matched MeSH terms: Dipeptidyl-Peptidase IV Inhibitors/administration & dosage*
Fulltext Strategies to Make Ramadan Fasting Safer in Type 2 Diabetics: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials and Observational Studies

Lee SW, Lee JY, Tan CS, Wong CP

Medicine (Baltimore), 2016 Jan;95(2):e2457.
PMID: 26765440 DOI: 10.1097/MD.0000000000002457

Ramadan is the holy month for Muslims whereby they fast from predawn to after sunset and is observed by all healthy Muslim adults as well as a large population of type 2 diabetic Muslims.To determine the comparative effectiveness of various strategies that have been used for type 2 diabetic Muslim who fast during Ramadan.A systematic review and network meta-analysis of randomized controlled studies (RCT) as well as observational studies for patients with type 2 diabetes who fasted during Ramadan was conducted. Eight databases were searched from January 1980 through October 2015 for relevant studies. Two reviewers independently screened and assessed study for eligibility, assessed the risk of bias, and extracted relevant data. A network meta-analysis for each outcome was fitted separately, combining direct and indirect evidence for each comparison.Twenty-nine studies, 16 RCTs and 13 observational studies each met the inclusion criteria. The most common strategy used was drug changes during the Ramadan period, which found that the use of DPP-4 (Dipeptidyl peptidase inhibitor -4) inhibitors were associated with a reduction in incidence of experiencing hypoglycemia during Ramadan in both RCTs (pooled relative risk: 0.56; 95% confidence interval: 0.44-0.72) as well as in observational studies (pooled relative risk: 0.27; 0.09-0.75). Ramadan-focused education was shown to be beneficial in reducing hypoglycemia in observational studies but not RCTs (0.25 versus 1.00). Network meta-analyses suggest that incretin mimetics can reduce the risk of hypoglycemia by nearly 1.5 times.The newer antidiabetic agents appear to lower the risk of hypoglycemia and improved glycemic control when compared with sulfonylureas. Ramadan-focused education shows to be a promising strategy but more rigorous examination from RCTs are required.

Matched MeSH terms: Dipeptidyl-Peptidase IV Inhibitors/administration & dosage*
Cost-effectiveness of dipeptidyl peptidase-4 inhibitor monotherapy versus sulfonylurea monotherapy for people with type 2 diabetes and chronic kidney disease in Thailand

Permsuwan U, Dilokthornsakul P, Thavorn K, Saokaew S, Chaiyakunapruk N

J Med Econ, 2017 Feb;20(2):171-181.
PMID: 27645706 DOI: 10.1080/13696998.2016.1238386

OBJECTIVE: With a high prevalence of chronic kidney disease (CKD) in type 2 diabetes (T2DM) in Thailand, the appropriate treatment for the patients has become a major concern. This study aimed to evaluate long-term cost-effective of dipeptidyl peptidase-4 (DPP-4) inhibitor monothearpy vs sulfonylurea (SFU) monotherapy in people with T2DM and CKD.
METHODS: A validated IMS CORE Diabetes Model was used to estimate the long-term costs and outcomes. The efficacy parameters were identified and synthesized using a systematic review and meta-analysis. Baseline characteristics and cost parameters were obtained from published studies and hospital databases in Thailand. Costs were expressed in 2014 US Dollars. Outcomes were presented as an incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to estimate parameter uncertainty.
RESULTS: From a societal perspective, treatment with DPP-4 inhibitors yielded more quality-adjusted life years (QALYs) (0.024) at a higher cost (>66,000 Thai baht (THB) or >1,829.27 USD) per person than SFU, resulting in the ICER of >2.7 million THB/QALY (>74,833.70 USD/QALY). The cost-effectiveness results were mainly driven by differences in HbA1c reduction, hypoglycemic events, and drug acquisition cost of DPP-4 inhibitors. At the ceiling ratio of 160,000 THB/QALY (4,434.59 USD/QALY), the probability that DPP-4 inhibitors are cost-effective compared to SFU was less than 10%.
CONCLUSIONS: Compared to SFU, DPP-4 inhibitor monotherapy is not a cost-effective treatment for people with T2DM and CKD in Thailand.

Matched MeSH terms: Dipeptidyl-Peptidase IV Inhibitors/administration & dosage

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