Glucagon-like peptide-1 receptor agonists or sodium-glucose cotransporter-2 inhibitors as add-on therapy for patients with type 2 diabetes? A systematic review and meta-analysis of surrogate metabolic endpoints.

OBJECTIVE: As sodium-glucose cotransporter-2 inhibitors (SGLT-2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are second-line treatment options in type 2 diabetes mellitus (T2DM), our study sought to provide precise effect estimates regarding the role of GLP-1RAs vs SGLT-2is as add-on treatments in patients uncontrolled by metformin monotherapy. RESEARCH DESIGN AND METHODS: PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL) and 'grey literature' were searched from their inception up to December 2019 for randomized controlled trials (RCTs) with durations≥12weeks to evaluate the safety and efficacy of adding a GLP-1RA vs an SGLT-2i in patients with T2DM. RESULTS: Three eligible RCTs were identified. Administration of GLP-1RAs vs SGLT-2is resulted in significant decreases in HbA1c with no significant impact on either body weight or fasting plasma glucose. GLP-1RA treatment led to a significant increase in odds for achieving an HbA1c<7% compared with SGLT-2is, whereas no difference was detected in body weight reductions of>5%. Significantly greater risk for any hypoglycaemia, nausea and diarrhoea, and lower risk for genital infections, was also observed with GLP-1RAs, while no differences regarding severe hypoglycaemia, treatment discontinuation and impact on blood pressure levels were identified. No other major safety issues arose. CONCLUSION: Our meta-analysis suggests that GLP-1RAs provide better glycaemic effects than SGLT-2is in patients with T2DM uncontrolled by metformin, albeit while increasing risk for hypoglycaemia and gastrointestinal adverse events.

Epidemiology and outcome of elderly admitted to the ward for sepsis.

BACKGROUND: The elderly represent a significant cohort of patients presenting at the emergency department, especially in the developed countries. They are characterized by impaired physical condition, comorbidities, and little immune system resources and make frequent use of the healthcare system and its facilities. This study aimed to describe the features and prognostic factors of sepsis in elderly patients (>60 years old) admitted to an internal medicine ward. MATERIAL AND METHODS: Two hundred eighty eight consecutively patients aged >60 years who were admitted with sepsis during a two-year-period were retrospectively included in the study. Clinical and laboratory parameters at presentation were analyzed. Causes of sepsis and biochemical markers were compared between the healthcare facility-naïve and the healthcare facility-exposed groups. The effect of comorbidities and previous exposure to the healthcare system on clinical course and outcome of the patients was analyzed. RESULTS: Among the comorbidities that were recorded and included in the analysis, the presence of chronic and acute renal impairment and neurologic disabilities were associated with a worse outcome of sepsis in the elderly. In the same cohort, a previous contact with the healthcare system was found to affect the duration of hospital stay, but not the outcome per se. Sepsis-related markers, such as inflammatory markers were not found to be associated with clinical progression and outcome. CONCLUSIONS: Timely diagnosis and accurate evaluation of the severity of sepsis is required to ensure a better outcome for the patients. Sensitive markers and accurate prognostic models are constantly pursued. The impact of living characteristics of the modern aging society is additionally addressed and their effect on sepsis outcome assessed. Hippokratia 2016, 20(4): 274-278.

Delay in starting insulin after failure of other treatments in patients with type 2 diabetes mellitus.

BACKGROUND AND AIM: In type 2 diabetes mellitus (T2DM), therapies to maintain blood glucose control usually fail after several years. The aim of this study was to estimate the time to insulin initiation, the glycemic burden that patients are exposed prior to conversion to insulin and their HbA1c level at that time and a year later. MATERIAL AND METHODS: Five hundred nine patients were included in this retrospective study. We identified patients with T2DM who started insulin therapy from 01/01/2002 to 30/06/2011, from the Scottish Care Information-Diabetes Collaboration (SCI-DC) database of Western General Hospital, Edinburgh, Scotland. We estimated the duration of diabetes prior to conversion to insulin therapy, the months they spent with glycated hemoglobin (HbA1c) above 7%, 8% or 9% until starting insulin, HbA1c and body weight (BW) at the time of conversion, at 6 and at 12 months before and after conversion. RESULTS: Patients started insulin therapy after a median period of 6.2 (1-30) years after diagnosis of T2DM. Median HbA1c was 10% (range 7.2-17.9) at the time of conversion, 8.8% (5. 8-16.9) at six months before and 8.3% (5.2-15) at 12 months before conversion, and 8.4% (4.7-14.3) at 6 months and 8.2% (5-14.7) at 12 months after conversion. Body weight (BW) was 86.6 kg (39.6-179.8) at the time of conversion and 91 kg (42.7-196) at 12 months after conversion. Patients spent a median period of 49 (0-325) months with HbA1c >7%, 25 (0-163) months with HbA1c >8% and 10 (0-135) months with HbA1c >9%. Insulin treatment resulted in a decrease in HbA1c at 12 months of 1.8% (p<0.05) but in an increase in BW by 2.9 kg (p<0.05). CONCLUSION: Healthcare professionals delay the initiation of insulin in patients with type 2 diabetes until their HbA1c exceeds 10%. As a result, patients are exposed to a significant glycemic burden. Change in treatment improves their glycemic control for the next 12 months. Hippokratia 2014; 18 (4): 306-309.

Comparative efficacy of exenatide versus insulin glargine on glycemic control in type 2 diabetes mellitus patients inadequately treated with metformin monotherapy.

PURPOSE: Comparative efficacy of exenatide versus insulin glargine primarily on glucemic control, and secondarily on body mass index (BMI), lipid profile and blood pressure, in type 2 diabetes mellitus (T2DM) patients suboptimally treated with metformin monotherapy. MATERIAL/METHODS: Forty-seven inadequately treated T2DM patients on metformin assigned to exenatide (n=18) or insulin glargine (n=29) for 26 weeks. Glycosylated hemoglobin (HbA1c), serum lipids, BMI, systolic and diastolic blood pressure, and adverse events, including episodes of hypoglycemia and gastrointestinal symptoms, were recorded. RESULTS: Either treatment had a similar favorable mean reduction in HbA1c. However, more patients in exenatide group achieved HbA1c ≤ 7% at the 26th week compared with insulin glargine group (p=0.036). Insulin glargine group had significantly more episodes of hypoglycemia compared with exenatide group (p=0.039). Gastrointestinal adverse events were non-significantly higher in the exenatide group. A significantly greater BMI reduction was observed in exenatide group, whereas ΒΜΙ was not altered in insulin glargine group. Total and LDL cholesterol (p=0.012), and triglycerides (p=0.016) significantly decreased, whereas HDL cholesterol increased (p=0.021) in the exenatide group, whereas only total cholesterol decreased in insulin glargine group. Changes in systolic and diastolic blood pressure were insignificant in both groups. CONCLUSIONS: Exenatide provided similar reduction in HbA1c, but fewer episodes of hypoglycemia, compared with insulin glargine. Exenatide had also a favorable effect on weight loss, although more gastrointestinal adverse events. Exenatide may provide a justified alternative in second line treatment of T2DM, but more trials are required to elucidate its long-term safety and cost-effectiveness.

Continuous subcutaneous insulin infusion versus multiple daily injections.

BACKGROUND AND AIM: Continuous Subcutaneous Insulin Infusion (CSII) and Multiple Daily insulin Injections (MDI) are both strategies aiming to achieve a tight glycemic and metabolic control. However, the choice between them remains controversial. The aim of the present study was to compare the efficacy of MDI (three or more injections daily) with CSII on glycemic control in patients with Type 1 Diabetes Mellitus and assess satisfaction from treatment in the CSII group. MATERIAL AND METHODS: Seventeen patients with Type 1 Diabetes Mellitus on CSII (previously on MDI) and 17 patients on MDI, matched for age, gender, BMI and duration of diabetes, were retrospectively studied. Glucosylated Hemoglobin A1c (HbA1c), frequency of hypoglycaemias (assessed as self reported episodes), BMI and total units of insulin per day were evaluated at baseline and after 6 months in both groups. CSII group completed a questionnaire concerning motive for treatment selection, advantages, deficiencies and inconvenience at the end of the study. Satisfaction from treatment was assessed with a scale from 0 to10. RESULTS: CSII group had more hypoglycaemic episodes at baseline than MDI group (16.2+/-2.8 vs 2.8+/-1.3, p<0,001). HbA1c (8.4+/-0.5 before vs 7.3+/-0.4 after, p<0.05) and total hypoglycaemic episodes per month (16.2+/-2.8 before vs 8.7+/-2.3 after, p<0.05) significantly decreased in CSII group 6 months after baseline. On the contrary, total hypoglycaemic episodes per month were increased in MDI group (2.8+/-1.3 before vs 10.8 +/-2,6 after, p<0.05) in order to maintain HbA1c levels. No significant differences were observed in BMI in both groups. Total insulin demands were reduced in the CSII group (49.4+/-3.3 before vs 39.0+/-4.6 after, p<0.05) and remained unchanged in MDI group. None of the patients discontinued CSII therapy, while overall satisfaction rate in this group was high. The main motive for CSII selection was frequent hypoglycaemic episodes and glucose fluctuations (10/17). The majority of patients expressed their wish for incorporating glucose trend indicator and/or continuous glucose measurement into pump and reducing pump size (15/17). Most commonly stated advantage was improved flexibility, followed by greater freedom and decreased sense of physical restrictions (10/17). Inconvenience mainly derived from alarm malfunction and catheter or needle occlusion and was reported from a minority of patients (4/17). CONCLUSION: CSII group reported more hypoglycaemias than MDI group at baseline but 6 months later had significantly less hypoglycaemic events, while on the contrary, MDI group 6 months after baseline had more frequent and more severe hypoglycaemias. Although baseline hypoglycaemias are not equal between the two groups, we can assume that CSII group achieved less hypoglycaemic events along with significant reduction in HbA1c while utilising less insulin units.