Brian Larsen Thorsted

Clinical Inertia in People With Type 2 Diabetes A retrospective cohort study of more than 80,000 people

OBJECTIVE To determine time to treatment intensification in people with type 2 diabetes treated with one, two, or three oral antidiabetes drugs (OADs) and associated levels of glycemic control. RESEARCH DESIGN AND METHODS This was a retrospective cohort study based on 81,573 people with type 2 diabetes in the U.K. Clinical Practice Research Datalink between January 2004 and December 2006, with follow-up until April 2011. RESULTS In people with HbA1c ≥7.0, ≥7.5, or ≥8.0% (≥53, ≥58, or ≥64 mmol/mol), median time from above HbA1c cutoff to intensification with an additional OAD was 2.9, 1.9, or 1.6 years, respectively, for those taking one OAD and >7.2, >7.2, and >6.9 years for those taking two OADs. Median time to intensification with insulin was >7.1, >6.1, or 6.0 years for those taking one, two, or three OADs. Mean HbA1c at intensification with an OAD or insulin for people taking one, two, or three OADs was 8.7, 9.1, and 9.7%. In patients taking one, two, or three OADs, median time from treatment initiation to intensification with an OAD or insulin exceeded the maximum follow-up time of 7.2 years. The probability of patients with poor glycemic control taking one, two, or three OADs, intensifying at end of follow-up with an OAD, was 21.1–43.6% and with insulin 5.1–12.0%. CONCLUSIONS There are delays in treatment intensification in people with type 2 diabetes despite suboptimal glycemic control. A substantial proportion of people remain in poor glycemic control for several years before intensification with OADs and insulin.

Hypoglycemia and Risk of Cardiovascular Disease and All-Cause Mortality in Insulin-Treated People With Type 1 and Type 2 Diabetes: A Cohort Study

OBJECTIVE Hypoglycemia has been associated with an increased risk of cardiovascular (CV) events and all-cause mortality. This study assessed whether, in a nationally representative population, there is an association between hypoglycemia, the risk of CV events, and all-cause mortality among insulin-treated people with type 1 diabetes or type 2 diabetes. RESEARCH DESIGN AND METHODS This retrospective cohort study used data from the Clinical Practice Research Datalink database and included all insulin-treated patients (≥30 years of age) with a diagnosis of diabetes. RESULTS In patients who experienced hypoglycemia, hazard ratios (HRs) for CV events in people with type 1 diabetes were 1.51 (95% CI 0.83, 2.75; P = ns) and 1.61 (1.17, 2.22), respectively, for those with and without a history of CV disease (CVD) before the index date. In people with type 2 diabetes, the HRs for patients with and without a history of CVD were 1.60 (1.21, 2.12) and 1.49 (1.23, 1.82), respectively. For all-cause mortality, HRs in people with type 1 diabetes were 1.98 (1.25, 3.17), and 2.03 (1.66, 2.47), respectively, for those with and without a history of CVD. Among people with type 2 diabetes, HRs were 1.74 (1.39, 2.18) and 2.48 (2.21, 2.79), respectively, for those with and without a history of CVD. The median time (interquartile range) from first hypoglycemia event to first CV event was 1.5 years (0.5, 3.5 years) and 1.5 years (0.5, 3.0 years), respectively, for people with type 1 and type 2 diabetes. CONCLUSIONS Hypoglycemia is associated with an increased risk of CV events and all-cause mortality in insulin-treated patients with diabetes. The relationship between hypoglycemia and CV outcomes and mortality exists over a long period.

Clinical inertia with regard to intensifying therapy in people with type 2 diabetes treated with basal insulin

To investigate whether clinical inertia, the failure to intensify treatment regimens when required, exists in people with type 2 diabetes treated with basal insulin.

Healthcare resource implications of hypoglycemia-related hospital admissions and inpatient hypoglycemia: retrospective record-linked cohort studies in England

Objective Using a retrospective cohort study, the mean length of hospital stay (LoS) and total per-patient expenditure for hypoglycemia requiring admission to hospital were estimated. In a separate matched retrospective cohort study, the effect of inpatient hypoglycemia on LoS, expenditure, and risk of all-cause mortality while admitted was investigated. Methods The cohorts consisted of patients aged ≥18 years with a diagnosis of type 1 or 2 diabetes between January 1, 2002 and October 30, 2012 in the Clinical Practice Research Datalink database, who had initiated insulin treatment and had a recording of hypoglycemia in the same period. In the matched retrospective cohort study, exposed patients (who experienced hypoglycemia in hospital) were case-matched with patients who did not experience hypoglycemia during admission (unexposed). Generalized linear regression was used to estimate LoS. Risk of all-cause mortality was evaluated via logistic regression. Results In the retrospective cohort study (1131 patients), mean LoS was 5.46 (95% CI 4.62 to 6.45) days for type 1 diabetes, and 5.04 (95% CI 4.46 to 5.71) days for type 2 diabetes. Mean cost per admission was £1034 (95% CI £855 to £1253). In the matched retrospective cohort study (1079 pairs of patients), exposed patients had a mean LoS of 11.91 days (95% CI 10.96 to 12.94 days) versus 4.80 (95% CI 4.41 to 5.23) for unexposed patients, p<0.0001. Exposed patients had a higher mortality risk compared with unexposed patients (OR 1.439 (95% CI 1.060to 1.952), p=0.0195). Total average per-patient cost for exposed patients was GBP (£)2235, 40% (p<0.0001) higher than total average admission cost in unexposed patients. Conclusions Hypoglycemia has a significant negative impact on patient outcomes, healthcare resource use, and expenditure.

Use and effectiveness of a fixed-ratio combination of insulin degludec/liraglutide (IDegLira) in a real-world population with type 2 diabetes: Results from a European, multicentre, retrospective chart review study

To describe the real‐world use and effectiveness of IDegLira, a fixed‐ratio combination of the basal insulin degludec, and the glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) liraglutide.

Self-reported hypoglycaemia in patients with type 2 diabetes treated with insulin in the Hoorn Diabetes Care System Cohort, the Netherlands: a prospective cohort study.

Background Our aim was to study the prevalence of self-reported hypoglycaemic sensations and its association with mortality in patients with type 2 diabetes (T2D) treated with insulin in usual care. Methods Demographics, clinical characteristics and mortality data were obtained from 1667 patients with T2D treated with insulin in the Hoorn Diabetes Care System Cohort (DCS), a prospective cohort study using clinical care data. Self-reported hypoglycaemic sensations were defined as either mild: events not requiring help; or severe: events requiring help from others (either medical assistance or assistance of others). The association between hypoglycaemic sensations and mortality was analysed using logistic regression analysis. Results At baseline, 981 patients (59%) reported no hypoglycaemic sensations in the past year, 612 (37%) reported only mild sensations and 74 (4%) reported severe hypoglycaemic sensations. During a median follow-up of 1.9 years, 98 patients (5.9%) died. Reporting only mild hypoglycaemic sensations was associated with a lower mortality risk (OR 0.48, 95% CI 0.28 to 0.80), while reporting severe sensations was not significantly associated with mortality (OR 0.76, 95% CI 0.33 to 1.80), compared with reporting no hypoglycaemic sensations, and adjusting for demographic and clinical characteristics. Sensitivity analyses showed an OR of 1.38 (95% CI 0.31 to 6.11) for patients reporting severe hypoglycaemic sensations requiring medical assistance. Conclusions Self-reported hypoglycaemic sensations are highly prevalent in our insulin-treated T2D population. Patients reporting hypoglycaemic sensations not requiring medical assistance did not have an increased risk of mortality, suggesting that these sensations are not an indicator of increased short-term mortality risk in patients with T2D.

Delay in treatment intensification increases the risks of cardiovascular events in patients with type 2 diabetes

A genetic risk score comprising common variants associated with fasting insulin is associated with OGTT- and clamp-based indices of whole body insulin sensitivityBackgrounds and aims: Diabetes mellitus (DM) and chronic kidney disease (CKD) are important risk factors for peripheral artery disease (PAD) and associated with a severely increased cardiovascular (CV) risk in these patients. DM increases production of AGEs and CKD decreases their clearance, while chronic low grade oxidative stress induces AGEs formation in both. However, human data on the role of tissue AGEs in PAD are scarce. We aimed to study the effects of DM and CKD on accumulation of tissue AGEs in patients with PAD. Materials and methods: We performed a cross-sectional study of 486 PAD patients at the outpatient clinic of Vascular Surgery. PAD was confirmed by angiography or duplex ultrasonography. CV risk factors and CV comorbidity (coronary artery disease [CAD], cerebrovascular disease [CVD], abdominal aortic aneurysm [AAA]) were assessed. Hypertension and hypercholesterolemia were defined as the use of blood pressure and lipid lowering drugs, respectively. Patients were divided into four groups based on the presence of DM and severity of CKD (> or 60 ml/min per 1.73 m2, P=0.0001. Conclusion: DM and CKD have additive effects on accumulation of tissue AGEs in PAD and are associated with the presence of CV comorbidity. Moreover, SAF predicts presence of CV comorbidity, independent of age, gender, DM and eGFR. Accelerated accumulation of AGEs may promote atherosclerosis and contribute to the severely increased CV risk in PAD patients with DM and CKD.

Clinical inertia in basal insulin-treated patients with type 2 diabetes – Results from a retrospective database study in Japan (JDDM 43)

Aims This retrospective cohort study investigated whether clinical inertia, the failure to intensify treatment when required, exists in Japanese clinical practice, using the CoDiC® database. How and when patients with type 2 diabetes treated with basal insulin received treatment intensification was also described. Materials and methods Patients with type 2 diabetes who initiated basal insulin between 2004 and 2011 were eligible for inclusion. Patients with an HbA1c ≥7.0% (≥53.0 mmol/mol) after 180 days of basal insulin titration were eligible for intensification, and their treatment was followed for up to 1.5 years. Endpoints were time to intensification, changes in HbA1c, and insulin dose. Results Overall, 2351 patients initiated basal insulin treatment (mean HbA1c 9.4% [79.2 mmol/mol]), and 1279 patients were eligible for treatment intensification (HbA1c ≥7.0% [≥53.0 mmol/mol]) after the 180-day titration period. During the 1.5-year follow-up period (beyond the 180-day titration period), 270 (21%) of these patients received treatment intensification. In patients receiving treatment intensification, mean HbA1c decreased from 8.6 to 8.2% (70.5 to 66.1 mmol/mol) at end of follow-up. Treatment was intensified using bolus insulin in 126 (47%) patients and with premixed insulin in 144 (53%) patients. The estimated probability of intensifying treatment during the 12 months after recording HbA1c ≥7.0% (≥53.0 mmol/mol) was 22.8%, and 27.5% after 17 months. Mean end-of-follow-up daily insulin dose was 35.11 units for basal–bolus compared with 20.70 units for premix therapy. Conclusions This study suggests clinical inertia exists in basal insulin-treated patients with type 2 diabetes in Japan. Strategies are needed to increase the number of patients undergoing therapy intensification and to reduce the delay in intensification in Japan.

Response to Comment on Khunti et al. Clinical Inertia in People With Type 2 Diabetes: A Retrospective Cohort Study of More Than 80,000 People. Diabetes Care 2013;36:3411–3417

We would like to thank Esposito et al. (1) for their interest in and comment on our article (2), in particular their recognition of the importance of the study and the significance of our results. Regarding their concern surrounding the definition of clinical inertia, there are several points that we would like to expand upon. First, we acknowledge that individualizing HbA1c targets may be needed for certain patients (e.g., the elderly) for whom balancing good glycemic control against the risk of hypoglycemia is even more important (3). HbA1c targets in treatment guidelines are only a recommendation. However, these clinical guidelines are used by physicians in practice, and as the …