Article

Impact of Hypoglycemia Associated With Antihyperglycemic Medications on Vascular Risks in Veterans With Type 2 Diabetes

School of Pharmacy, Saint Joseph College, Hartford, Connecticut, USA.
Diabetes care (Impact Factor: 8.57). 03/2012; 35(5):1126-32. DOI: 10.2337/dc11-2048
Source: PubMed

ABSTRACT Hypoglycemia is associated with failure to show cardiovascular benefit and increased mortality of intensive glycemic control in randomized clinical trials. This retrospective cohort study aimed to examine the impact of hypoglycemia on vascular events in clinical practice.
Patients with type 2 diabetes were identified by ICD-9-CM codes (250.xx except for 250.x1 and 250.x3) between 1 January 2004 and 1 September 2010 from the Veterans Integrated Service Network 16. Index date was defined as the first date of new antihyperglycemic medications (index treatment). Patients with 1-year preindex records of hypoglycemia, cardiovascular, and microvascular diseases were excluded. The hypoglycemia group was identified by ICD-9-CM codes (250.8, 251.0, 251.1, and 251.2) within the index treatment period. A propensity score-matched group was used as control subjects. Cardiovascular events, microvascular complications, and all-cause death were compared using Kaplan-Meier analysis and Cox proportional hazards regression model.
Among the unmatched sample (N = 44,261), the hypoglycemia incidence rate was 3.57/100 patient-years. The matched sample (hypoglycemia group: n = 761; control group: n = 761) had a median follow-up of 3.93 years, mean age of 62.6 ± 11.0 years, and preindex HbA(1c) of 10.69 ± 2.61%. The 1-year change in HbA(1c) was similar (hypoglycemia group -0.51 vs. control group -0.32%, P = 0.7244). The hypoglycemia group had significantly higher risks of cardiovascular events (hazard ratio 2.00 [95% CI 1.63-2.44]) and microvascular complications (1.76 [1.46-2.11]) but no statistical mortality difference. Patients with at least two hypoglycemic episodes were at higher risks of vascular events than those with one episode (1.53 [1.10-1.66]).
Hypoglycemia is associated with higher risks of incident vascular events. Patients with hypoglycemia should be monitored closely for vascular events.

0 Followers
 · 
137 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: AimsThe EUREXA trial extension evaluated third-line thiazolidinedione or glimepiride therapy in patients inadequately controlled on metformin + exenatide twice daily (BID), and third-line exenatide BID in patients inadequately controlled on metformin + glimepiride.Materials and methodsIn this randomized, open-label, multicenter trial, 144 patients with type 2 diabetes inadequately controlled (glycated hemoglobin [HbA1c] >9% [75 mmol/mol] after 3 months’ treatment or >7% [53 mmol/mol] at 2 consecutive visits 3 months apart after 6 months’ treatment) on metformin + exenatide BID were re-randomized to add-on thiazolidinedione or glimepiride, and 166 patients inadequately controlled on metformin + glimepiride received add-on exenatide BID. Changes in HbA1c, body mass index (BMI), lipids, hypoglycemia, and vital signs were evaluated.ResultsMedian triple therapy duration was ~2 years. In patients inadequately controlled on metformin + exenatide BID, add-on thiazolidinedione decreased HbA1c significantly better than add-on glimepiride (130-week difference 0.48%, 95% CI 0.19–0.77 [5.2 mmol/mol, 2.1–8.4], p = 0.001), but with significantly increased BMI and systolic blood pressure. Ratio of documented symptomatic (blood glucose ≤70 mg/dl) hypoglycemia rates for add-on glimepiride to add-on thiazolidinedione was 8.48 (p < 0.0001). Add-on exenatide BID after metformin + glimepiride significantly reduced HbA1c (mean [SD] change from baseline −0.35 [0.89]% [−3.8 (9.7) mmol/mol]) and BMI (−0.82 [1.9] kg/m2) at 130 weeks, with a slightly increased rate of documented symptomatic hypoglycemia from metformin + glimepiride (ratio 1.49).Conclusions Thiazolidinedione, but not glimepiride, was an effective and well tolerated third-line therapy in patients without glycemic control after long-term therapy with metformin + exenatide BID. Exenatide BID was an effective and well tolerated third-line therapy in patients inadequately controlled on metformin + glimepiride.(NCT00359762)
    Diabetes Obesity and Metabolism 04/2015; DOI:10.1111/dom.12471 · 5.46 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Glucose-lowering therapy with dipeptidyl peptidase-4 (DPP-4) inhibitors is associated with a low risk of hypoglycaemia. We hypothesise that DPP-4 inhibition prevents hypoglycaemia via increased glucagon counterregulation through the incretin hormone glucose-dependent insulinotropic polypeptide (GIP). Using a hyperinsulinaemic-hypoglycaemic clamp that targeted 2.5 mmol/l we examined the effects of the DPP-4 inhibitor vildagliptin and GIP infusion on steady state glucose infusion rate (GIR) and glucagon counterregulation in mice. Following up on this, we performed a hyperinsulinaemic-hypoglycaemic clamp in mice carrying a genetic deletion of the GIP receptor (GIPR (-/-) mice) or the glucagon receptor (GCGR (-/-) mice). GIR was reduced by 89.0 ± 3.1% (p = 7.0 × 10(-6)) by vildagliptin and by 38.8 ± 12.6% (p = 0.040) by GIP in wild-type (wt) mice, whereas GIR was increased both in GIPR (-/-) (to 33.0 ± 6.8 from 14.0 ± 2.9 μmol kg (-1) min (-1); p = 0.017) and in GCGR (-/-) mice (to 59.4 ± 1.1 from 16.5 ± 2.4 μmol kg (-1) min (-1); p = 8.2 × 10(-7)) compared with wt. By contrast, neither vildagliptin nor GIP had any effect on GIR in GCGR (-/-) mice. Furthermore, vildagliptin increased intact GIP four- to eightfold during hypoglycaemia and the counterregulatory increase in glucagon levels during hypoglycaemia was augmented by vildagliptin (incremental AUC [iAUC] during clamp was 99.2 ± 22.5 vs 42.0 ± 4.5 pmol/l × min in controls; p = 0.039) and GIP (iAUC of fold change during clamp was 372 ± 81 vs 161 ± 40 FC × min with saline; p = 0.031). Based on these results we propose that DPP-4 inhibition protects from hypoglycaemia by augmenting glucagon counterregulation through a GIP-glucagon counterregulatory axis.
    Diabetologia 02/2015; 58(5). DOI:10.1007/s00125-015-3518-7 · 6.88 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective Patients may fear the symptoms and consequences associated with hypoglycemia. We tested whether fear of hypoglycemia is independently associated with poorer health-related quality of life (HRQOL).Research design and methodsData were collected using direct-mail survey and enrollment information from adult commercial health plan enrollees with type 2 diabetes during a 12-month period (12/01/2008 to 11/30/2009). HRQOL was evaluated by the EuroQol (EQ)¿5D index and 12-item Short Form Health Survey Mental Component Summary (SF-12 MCS) and Physical Component Summary (SF-12 PCS). Fear of hypoglycemia was assessed using the Hypoglycemia Fear Survey (HFS). Two ordinary least-squares (OLS) models of HRQOL controlling for demographics and illness characteristics were specified, and OLS regression coefficients and statistical inferences were compared. Model 1 included 1 variable of hypoglycemia symptoms; Model 2 included both hypoglycemia symptoms and HFS score.ResultsOf 3999 patients contacted, 813 responded to the survey. Model 1: hypoglycemia symptoms alone were associated with worse HRQOL (SF-12 MCS and SF-12 PCS scores and EQ-5D utility score; all P¿<¿0.05). Model 2: hypoglycemia symptoms were significantly associated only with SF-12 MCS score. HFS total score was significantly associated with all 3 HRQOL scores. Hypoglycemia symptoms, Hispanic ethnicity, and longer diabetes duration were associated with greater hypoglycemia fear. Higher income, white race, and treatment without sulfonylurea or insulin were associated with less hypoglycemia fear (all P¿<¿0.05).Conclusions In addition to the effect of symptomatic hypoglycemia on HRQOL, fear of hypoglycemia was independently associated with lower overall health status and mental and physical health.
    Health and Quality of Life Outcomes 11/2014; 12(1):167. DOI:10.1186/s12955-014-0167-3 · 2.10 Impact Factor

Full-text (3 Sources)

Download
76 Downloads
Available from
Jun 3, 2014