Dataset Information

Impact of differing glucose-lowering regimens on the pattern of association between glucose control and survival.

ABSTRACT:

Aims

To characterize survival in relation to achieved glycated haemoglobin (HbA1c) level within alternative glucose-lowering regimens with differing risks of hypoglycaemia.

Methods

Data were extracted from the UK Clinical Practice Research Datalink and the corresponding Hospital Episode Statistics. Patients with type 2 diabetes prescribed glucose-lowering therapy in monotherapy or dual therapy with metformin between 2004 and 2013 were identified. Risk of all-cause mortality within treatment cohorts was evaluated using the Cox proportional hazards model, introducing mean HbA1c as a quarterly updated, time-dependent covariable.

Results

There were 6646 deaths in a total follow-up period of 374?591?years. Survival for lower (<7%) vs moderate HbA1c levels (?7%, <8.5%) differed by cohort: metformin, adjusted hazard ratio (aHR) 1.03 (95% confidence interval [CI] 0.95-1.12); sulphonylurea, aHR 1.11 (95% CI 0.99-1.25); insulin, aHR 1.47 (95% CI 1.25-1.72); combined regimens with low hypoglycaemia risk, aHR 1.02 (95% CI 0.94-1.10); and combined regimens with higher hypoglycaemia risk excluding insulin, aHR 1.24 (95% CI 1.13-1.35) and including insulin, aHR 1.28 (95% CI 1.18-1.37). Higher HbA1c levels were associated with increased mortality in regimens with low hypoglycaemia risk. Post hoc analysis by HbA1c deciles revealed an elevated risk of all-cause mortality for the lowest deciles across all cohorts, but particularly in those regimens associated with hypoglycaemia. High HbA1c was associated with no difference, or a small increase in mortality risk in regimens with increased risk of hypoglycaemia.

Conclusions

The pattern of mortality risk across the range of HbA1c differed by glucose-lowering regimen. Lower HbA1c was associated with increased mortality risk compared with moderate control, especially in those regimens associated with hypoglycaemia. High levels of HbA1c were associated with the expected elevated mortality risk in regimens with low hypoglycaemia risk.

SUBMITTER: Currie CJ

PROVIDER: S-EPMC5888185 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Impact of differing glucose-lowering regimens on the pattern of association between glucose control and survival.

Currie Craig J CJ Holden Sarah E SE Jenkins-Jones Sara S Morgan Christopher Ll CL Voss Bernd B Rajpathak Swapnil N SN Alemayehu Berhanu B Peters John R JR Engel Samuel S SS

Diabetes, obesity & metabolism 20171208 4

<h4>Aims</h4>To characterize survival in relation to achieved glycated haemoglobin (HbA1c) level within alternative glucose-lowering regimens with differing risks of hypoglycaemia.<h4>Methods</h4>Data were extracted from the UK Clinical Practice Research Datalink and the corresponding Hospital Episode Statistics. Patients with type 2 diabetes prescribed glucose-lowering therapy in monotherapy or dual therapy with metformin between 2004 and 2013 were identified. Risk of all-cause mortality within ...[more]

PMID: 29119713

Similar Datasets

Project description:Background & aimsGlucose-lowering drug is associated with various cancers, but the causality with gastrointestinal cancer risk is rarely reported. We aimed to explore the causality between them in this Mendelian randomization (MR) study.MethodsTwo-sample MR, summary-data-based (SMR), mediation MR, and colocalization analyses was employed. Ten glucose-lowering drug targets (PPARG, DPP4, GLP1R, INSR, SLC5A2, ABCC8, KCNJ11, ETFDH, GPD2, PRKAB1) and seven types of gastrointestinal cancer (anal carcinoma, cardia cancer, gastric cancer, hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), pancreatic cancer, rectum cancer) were included. Patients with gastrointestinal cancers from six different large GWAS databases, including the UK Biobank and Finnish cohorts were incorporated, for discovery and external validation. Meta-analysis was employed to integrate the results from both discovery and validation cohorts, thereby ensuring the reliability of findings.ResultsABCC8/KCNJ11 were associated with pancreatic cancer risk in both two-sample MR (odds ratio (OR): 15.058, per standard deviation unit (SD) change of glucose-lowering durg target perturbation equivalent to 1 SD unit of HbA1c lowering; 95% confidence interval (95% CI): 3.824-59.295; P-value = 0.0001) and SMR (OR: 1.142; 95% CI: 1.013-1.287; P-value = 0.030) analyses. The mediation effect of body mass index (OR: 0.938; 95% CI: 0.884-0.995; proportion of mediation effect: 3.001%; P-value = 0.033) on ABCC8/KCNJ11 and pancreatic cancer was uncovered. Strong connections of DPP4 with anal carcinoma (OR: 0.123; 95% CI: 0.020-0.745; P-value = 0.023) and ICC (OR: 7.733; 95% CI: 1.743-34.310; P-value = 0.007) were detected. PPARG was associated with anal carcinoma (OR: 12.909; 95% CI: 3.217-51.795; P-value = 0.0003), HCC (OR: 36.507; 95% CI: 8.929-149.259; P-value < 0.0001), and pancreatic cancer (OR: 0.110; 95% CI: 0.071-0.172; P-value < 0.0001). SLC5A2 was connected with pancreatic cancer (OR: 8.096; 95% CI: 3.476-18.857; P-value < 0.0001). Weak evidence indicated the connections of GLP1R, GPD2, and PRKAB1 with anal carcinoma, cardia cancer, ICC, and rectum cancer. In addition, the corresponding results were consistently validated in both the validation cohorts and the integrated outcomes.ConclusionsSome glucose-lowering drugs were associated with gastrointestinal cancer risk, which might provide new ideas for gastrointestinal cancer treatment.

Project description:BackgroundInformation regarding the use of glucose-lowering medications in patients with chronic kidney disease (CKD) is limited.Study designRetrospective cohort study.Setting & participantsMedicare 5% random sample of patients with CKD with type 2 diabetes, 2007 to 2016.PredictorsStudy year, CKD stage, low-income subsidy status, and demographic characteristics (age, sex, and race/ethnicity).OutcomesTrends in use of glucose-lowering medications.Analytical approachYearly cohorts of patients with CKD and type 2 diabetes were created. Descriptive statistics were used to report proportions of patients using glucose-lowering medications. To test overall trends in glucose-lowering medication classes, linear probability models with adjustment for age, sex, race/ethnicity, CKD stage, and low-income subsidy status were used.ResultsMetformin use increased significantly from 32.7% in 2007 to 48.7% in 2016. Use of newer classes of glucose-lowering medications increased significantly, including dipeptidyl peptidase 4 inhibitors (5.6%, 2007; 21.7%, 2016), glucagon-like peptide 1 receptor agonists (2.3%, 2007; 6.1%, 2016), and sodium-glucose cotransporter 2 inhibitors (0.2%, 2013; 3.3%, 2016). Newer insulin analogue use increased from 37.2% in 2007 to 46.3% in 2013 and then remained steady. Use of sulfonylureas, thiazolidinediones, older insulins (human regular and neutral protamine Hagedorn), α-glucosidase inhibitors, amylin mimetics, and meglitinides decreased significantly. Insulin was the most highly used single medication class. Insulin use was higher among low-income subsidy than among non-low-income subsidy patients. Combination therapy was less common as CKD stage increased.LimitationsPatients with CKD and type 2 diabetes and the CKD stages were identified with diagnosis codes and could not be verified through medical record review. Our results may not be generalizable to younger patients with CKD with type 2 diabetes.ConclusionsUse of metformin and newer glucose-lowering medication classes is increasing in patients with CKD with type 2 diabetes. We anticipate that percentages of patients with CKD using these newer agents will increase.

Dataset Information

Impact of differing glucose-lowering regimens on the pattern of association between glucose control and survival.

Aims

Methods

Results

Conclusions

Publications

Impact of differing glucose-lowering regimens on the pattern of association between glucose control and survival.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets