Lauge Østergaard

Treatment potential of the GLP-1 receptor agonists in type 2 diabetes mellitus: a review

ABSTRACT Over the last decade, the discovery of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) has increased the treatment options for patients with type 2 diabetes mellitus (T2DM). GLP-1 RAs mimic the effects of native GLP-1, which increases insulin secretion, inhibits glucagon secretion, increases satiety and slows gastric emptying. This review evaluates the phase III trials for all approved GLP-1 RAs and reports that all GLP-1 RAs decrease HbA1c, fasting plasma glucose, and lead to a reduction in body weight in the majority of trials. The most common adverse events are nausea and other gastrointestinal discomfort, while hypoglycaemia is rarely reported when GLP-1 RAs not are combined with sulfonylurea or insulin. Treatment options in the near future will include co-formulations of basal insulin and a GLP-1 RA.

Long-term causes of death in patients with infective endocarditis who undergo medical therapy only or surgical treatment: a nationwide population-based study

OBJECTIVES It is known that patients surviving infective endocarditis have a poor long-term prognosis; however, few studies have addressed the long-term causes of death in patients surviving the initial hospitalization. METHODS Using Danish administrative registries, we identified patients admitted to a hospital with 1st time infective endocarditis in the period from January 1996 to December 2014, who were alive at the time of discharge. The study population was categorized into (i) patients undergoing medical therapy only and (ii) patients undergoing surgical and medical treatment. We examined the cardiovascular and non-cardiovascular causes of death. Using the Cox analysis, we investigated the associated risk of dying from a specific prespecified cause of death (heart failure, infective endocarditis and stroke) within the surgery group when compared with the medically treated group. RESULTS We identified 5576 patients: 4220 patients belonged to the medically treated group and 1356 patients to the surgery group. At the 10-year follow-up, the mortality rate was 63.1% and 41.6% in the medically treated group and the surgery group, respectively. Cardiovascular disease was the most frequent cause of death in both groups accounting for 52.5% in the medically treated group and 55.2% in the surgery group. Patients undergoing surgery were associated with a lower risk of dying from heart failure and stroke when compared with medically treated patients [hazard ratio = 0.66 (95% confidence interval: 0.46-0.94) and hazard ratio = 0.59 (95% confidence interval: 0.37-0.96), respectively]. CONCLUSIONS No major differences were found in the main causes of death between groups. Patients in the surgical group were associated with a lower risk of dying from heart failure and stroke when compared with medically treated patients.

Fixed-ratio combination therapy with GLP-1 receptor agonist liraglutide and insulin degludec in people with type 2 diabetes

ABSTRACT Introduction: A fixed combination of basal insulin degludec and glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide (IDegLira; 50 units degludec/1.8 mg liraglutide) has been developed as a once daily injection for the treatment of type 2 diabetes (T2D). In the phase 3a trial programme ‘Dual action of liraglutide and insulin degludec in type 2 diabetes’ (DUAL™), five trials of 26 weeks duration and one trial of 32 weeks duration have evaluated the efficacy and safety of IDegLira compared with administration of insulin degludec, insulin glargine, liraglutide alone or placebo. Areas covered: Combination therapy with IDegLira reduces HbA1c more than monotherapy with a GLP-1RA (liraglutide) or insulin (degludec or glargine). Combination therapy leads also to weight loss, or a stable body weight, with no increase in hypoglycaemia. Rates of adverse events did not differ between treatment groups; however, gastrointestinal side effects were fewer with IDegLira compared with liraglutide treatment alone. A limitation of the DUAL™ development programme is that patients receiving basal insulin doses in excess of 50 units were excluded from the studies. Expert commentary: In conclusion, IDegLira combines the clinical advantages of basal insulin and GLP-1RA treatment, and is a treatment strategy that could improve the management of patients with T2D.

Temporal changes in infective endocarditis guidelines during the last 12 years: High-level evidence needed

Background Infective endocarditis (IE) is a complex disease necessitating extensive clinical guidelines. The guidelines from the American Heart Association (AHA) and the European Society of Cardiology (ESC) have been markedly extended during the last 12 years. We examined the evidence base for these changes. Methods IE guidelines published by AHA and ESC were reviewed. We categorized and combined guidelines into 3 time periods: (1) 2004 (AHA) and 2005 (ESC), (2) 2007 (AHA) and 2009 (ESC), and (3) 2015 (AHA) and 2015 (ESC). Number of recommendations, classes of recommendations (I, II, or III), and levels of evidence (LOE) (A, B, or C) were assessed and the changes over time. Results From period 1 to period 3, we found a statistically significant increase in total number of IE recommendations from 37 to 253 (P < .01), a 6.8‐fold increase. There were a significant decrease in LOE A (from 7 [20.0%] in period 1 to 4 [1.6%] in period 3, P < .0001, a 57% decrease), a nonsignificant decrease in LOE B recommendations (from 17 [48.6%] in period 1 to 115 [45.9%] in period 3, P = .29, a 6.8‐fold increase), and a significant increase in LOE C recommendations (from 11 [31.4%] in period 1 to 134 [53.0%] in period 3, P = .02, a 12.2‐fold increase). Conclusions The number of IE guideline recommendations has increased 6‐ to 7‐fold during the last decade without a corresponding increase in evidence. These results highlight the strong need for more clinical studies to improve the level of evidence in IE guidelines.

The Role of Antiplatelet Therapy in Primary Prevention. A Review

The efficacy of antiplatelet therapy for the secondary prevention of cardiovascular disease after an ischemic event is well established. However, the role for antiplatelet therapy for the primary prevention of cardiovascular disease is more complex because of the interplay of efficacy vs safety in individuals without established cardiovascular disease who have a relatively low, but linear trajectory of cardiovascular risk. Several large randomized trials have investigated the efficacy and safety of antiplatelet therapy (primarily aspirin) for patients without established cardiovascular disease. The pharmacological profile of the most commonly used primary prevention antiplatelet agent, aspirin, has been delineated by randomized clinical trials and showcased in practice guidelines for reducing cardiovascular risk. For this indication, aspirin has been consistently shown to reduce the risk of non-fatal myocardial infarction with little impact on cardiovascular death, but with a consistent increased risk of bleeding. These divergent results have contributed to differences in the recommendations from international practice guidelines and highlight controversy at the forefront of considerations for anti-platelet therapy for primary prevention. However, further studies in specific sub-groups of patients without established cardiovascular disease such as those with Diabetes Mellitus, chronic kidney disease, or the elderly may clarify which patient groups will benefit the most from aspirin treatment for the primary prevention of a cardiovascular event.

Duration and complications of diabetes mellitus and the associated risk of infective endocarditis

BACKGROUND Long duration of diabetes mellitus (DM) is associated with an increased risk of infection, however no studies have yet focused on the duration of DM and the associated risk of infective endocarditis (IE). METHODS Patients with DM were identified through the Danish Prescription Registry, 1996-2015. Duration of DM was split in follow-up periods of: 0-5 years, 5-10 years, 10-15 years, and >15 years. Multivariable adjusted Poisson regression was used to calculate incidence rate ratios (IRR) according to study groups. DM late-stage complications and the associated risk of IE were investigated as time-varying covariates using the validated Diabetes Complications Severity Index (DCSI). RESULTS We included 299,551 patients with DM. In patients with DM duration of 0-5 years, 5-10 years, 10-15 years, and >15 years, the incidence rates of IE were 0.24, 0.33, 0.58, and 0.96 cases of IE/1000 person years, respectively. Patients with DM duration 5-10 years, 10-15 years, and >15 years were associated with a higher risk of IE with an IRR of 1.24 (95% CI: 1.02-1.51), 1.92 (95% CI: 1.52-2.43) and 3.05 (95% CI: 2.11-4.40), respectively, compared with DM duration 0-5 years. Patients with a DCSI score of 2, 3 and >3 were associated with a higher risk of IE compared with patients with a DCSI score of 0, IRR = 1.78 (95% CI: 1.34-2.36), IRR = 2.34 (95% CI: 1.73-3.16), and IRR = 2.59 (95% CI: 1.92-3.48), respectively. CONCLUSION This study shows a stepwise increase in the risk of IE with DM duration and severity independent of age and known comorbidity.

Return to the workforce following infective endocarditis—A nationwide cohort study

Background The ability to return to work after infective endocarditis (IE) holds important socioeconomic consequences for both patients and society, yet data on this issue are sparse. We examined return to the workforce and associated factors in IE patients of working age. Methods Using Danish nationwide registries, we identified 1,065 patients aged 18–60 years with a first‐time diagnosis of IE (1996–2013) who were part of the workforce prior to admission and alive at discharge. Results One year after discharge, 765 (71.8%) patients had returned to the workforce, 130 (12.2%) were on paid sick leave, 76 (7.1%) received disability pension, 23 (2.2%) were on early retirement, 65 (6.1%) had died, and 6 (0.6%) had emigrated. Factors associated with return to the workforce were identified using multivariable logistic regression. Younger age (18–40 vs 56–60 years; odds ratio, 2.85; 95% CI, 1.71–4.76) and higher level of education (higher educational level vs basic school; 5.47, 2.05–14.6) and income (highest quartile vs lowest; 3.17, 1.85–5.46) were associated with return to the workforce. Longer length of hospital stay (>90 vs 14–30 days; 0.16, 0.07–0.38); stroke during IE admission (0.38, 0.21–0.71); and a history of chronic kidney disease (0.29, 0.11–0.75), chronic obstructive pulmonary disease (0.31, 0.13–0.71), and malignancy (0.39, 0.22–0.69) were associated with a lower likelihood of returning to the workforce. Conclusions Seven of 10 patients who were part of the workforce prior to IE and alive at discharge were part of the workforce 1 year later. Younger age, higher socioeconomic status, and absence of major comorbidities were associated with return to the workforce.

RISK FACTORS ASSOCIATED WITH INFECTIVE ENDOCARDITIS AFTER AORTIC VALVE REPLACEMENT

Background: Patients undergoing aortic valve replacement (AVR) are considered at subsequent risk of infective endocarditis (IE), yet data on incidence of IE and associated factors are sparse. Methods: Using nationwide registries in Denmark, all patients with no prior or current history of IE who