Association between variants in TCF7L2, CTRB1/2, and GLP-1R genes and response to therapy with glucagon-like peptide-1 receptor agonists.

OBJECTIVES: The factors determining the response to treatment with glucagon-like peptide-1 receptor agonists (GLP-1- RAs) have not been clarified. The present study investigated the association between polymorphisms in TCF7L2, CTRB1/2, and GLP-1 R genes and response to GLP-1 RAs regarding glycemic control and weight loss among Greek patients with type 2 diabetes mellitus (T2DM). METHODS: Patients (n = 191) treated with GLP-1 RAs for at least 6 months were included. Participants were genotyped for TCF7L2 rs7903146 (C>T), CTRB1/2 rs7202877 (T>G) and GLP-1 R rs367543060 (C>T) polymorphisms. Clinical and laboratory parameters were measured before, 3, and 6 months after treatment initiation. The patients were classified into responders and non-responders according to specific criteria. RESULTS: Carriers of at least one rs7903146 'T' allele and rs7202877 'G' allele presented similar glucose control and weight loss response to GLP-1 RAs with the respective homozygous wild-type genotypes [odds ratio (OR): 1.08, 95% confidence interval (CI): 0.5, 2.31, p = 0.85 and OR: 1.35, 95% CI: 0.66, 2.76, p = 0.42; OR: 1.4, 95% CI: 0.56, 3.47, p = 0.47 and OR: 1.28, 95% CI: 0.55, 2.98, p = 0.57, respectively]. Regarding the GLP-1 R polymorphism, all participants were homozygous for the wild-type allele; thus, no comparisons were feasible. Female sex (p = 0.03) and lower baseline weight (p = 0.024) were associated with an improved glycemic and weight loss response, respectively. CONCLUSION: There is no evidence suggesting a role for the variants studied in response to GLP-1 RA therapy in people with T2DM. However, specific demographic and clinical factors may be related to a better response to treatment with these agents.

Clinical and Genetic Predictors of Glycemic Control and Weight Loss Response to Liraglutide in Patients with Type 2 Diabetes.

Background: Evidence suggests a heterogeneous response to therapy with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes mellitus (T2DM). The aim of this study is to identify the genetic and clinical factors that relate to glycemic control and weight loss response to liraglutide among patients with T2DM. Methods: The medical records of 116 adults with T2DM (51% female, mean body mass index 35.4 ± 6.4 kg/m2), who had been on treatment with liraglutide for at least 6 months and were genotyped for CTRB1/2 rs7202877 (T > G) polymorphism, were evaluated. Clinical and laboratory parameters were measured at baseline, 3, and 6 months after initiating liraglutide treatment. The good glycemic response was defined as one of the following: (i) achievement of glycated hemoglobin (HbA1c) < 7% (ii) reduction of the baseline HbA1c by ≥1%, and (iii) maintenance of HbA1c < 7% that a patient already had before switching to liraglutide. Weight loss responders were defined as subjects who lost ≥3% of their baseline weight. Results: Minor allele frequency was 16%. Individuals were classified as glycemic control and weight loss responders (81 (70%) and 77 (66%), respectively). Carriers of the rs7202877 polymorphic allele had similar responses to liraglutide treatment in terms of glycemic control (odds ratio (OR): 1.25, 95% confidence interval (CI): 0.4, 3.8, p = 0.69) and weight loss (OR: 1.12, 95% CI: 0.4, 3.2, p = 0.84). In the multivariable analysis, higher baseline HbA1c (adjusted OR: 1.45, 95% CI: 1.05, 2.1, p = 0.04) and lower baseline weight (adjusted OR: 0.97, 95% CI: 0.94, 0.99, p = 0.01) were associated with better glycemic response to liraglutide, while higher baseline weight was associated with worse weight response (adjusted OR: 0.97, 95% CI: 0.95, 0.99, p = 0.02). Conclusions: Specific patient features can predict glycemic and weight loss response to liraglutide in individuals with T2DM.

Adherence to the National Guidelines for Follow-Up Protocol in Subjects with Type 2 Diabetes Mellitus in Greece: The GLANCE Study.

INTRODUCTION: Physician adherence, or lack therefore, to diabetes care and follow-up guidelines may be linked to the rates of achieving suboptimal glycaemic, blood pressure and lipid targets in people with type 2 diabetes mellitus (T2DM). In this cross-sectional study we evaluated physician adherence to the patient follow-up protocol (PFP) of the 2017 Hellenic Diabetes Association (HDA) guidelines and also assessed glycated haemoglobin (HbA1c), blood pressure and lipid control achievement rates in the routine care setting in Greece. METHODS: Eligible subjects were adults with T2DM receiving oral hypoglycaemic agents (OHAs) for ≥ 1 year who had ≥ 2 HbA1c measurements in the previous year and an HbA1c target < 7%. Overall adherence at the subject level was defined as the percentage of the 62 HDA PFP items that had been met during the past year. RESULTS: Between June and December 2018, 601 eligible subjects (54.6% men; mean age 65.2 years; median T2DM duration 5.9 years, of whom 96.5% had ≥ 1 medical condition/comorbidity), were enrolled into the study by 53 hospital- and office-based endocrinologists, internists and general practitioners. The main OHAs prescribed at enrolment were metformin (91.0%), dipeptidyl peptidase-4 inhibitors (60.7%), sodium-glucose co-transporter-2 inhibitors (23.5%) and sulphonylureas (16.3%). Mean overall physician adherence to the PFP was 43.6%. Predictors of greater higher physicans' adherence were female sex (p = 0.026), > 3 medical conditions/comorbidities (p = 0.043) and diabetic complications (p < 0.001). HbA1c, low-density lipoprotein-cholesterol, systolic/diastolic blood pressure and composite metabolic targets were achieved by 82.1, 57.0, 42.6 and 21.6% of subjects, respectively. CONCLUSIONS: In Greek routine care, physician adherence to the PFP of the 2017 HDA guidelines is suboptimal. Future efforts should focus on identifying the barriers to an adequate adherence by physicians to the full PFP, with the aim to provide optimal patient care.

Lessons From a Diabetes Clinic: Achieving Glycemic Goals and Clinical Use of Antidiabetic Agents in Patients With Type 2 Diabetes.

The proportion of patients with type 2 diabetes who achieve their glycemic goals remains low. We examined medical records and A1C results from patient visits to our referral diabetes center between 21 March to 20 July 2018. After stratifying patients into four groups-monotherapy, dual therapy, triple therapy, or insulin therapy-we found that the target A1C of ≤7.0% was achieved by 86% of patients and that A1C was uniformly low across the treatment categories. Our individualized approach, which included high use of glucagon-like peptide-1 receptor agonists and low use of sulfonylureas, may have contributed to these results.

Fasting insulin levels correlate with the frequency of hypoglycemic events in people with type 2 diabetes on treatment with sulfonylureas: A pilot study.

AIMS AND OBJECTIVES: We aimed to explore whether fasting insulin levels correlate with the risk of hypoglycemia in people with Type 2 diabetes (T2D) receiving sulfonylureas (SUs). MATERIALS AND METHODS: Our study included 58 individuals with T2D who had been on treatment with SUs, but not insulin, for more than 2 years. Confirmed hypoglycemic episodes during the past year were self-reported by the patients, and a potential relationship of hypoglycemic event frequency with fasting insulin levels was investigated. RESULTS: Fasting insulin concentrations were found to have a low positive and statistically significant correlation with the number of cases of mild hypoglycemia per year (ρ = 0.279/P = 0.034) and a moderately positive and statistically significant correlation with the number of severe hypoglycemic events per month (ρ = 0.349/P = 0.007) and per year (ρ = 0.39/P = 0.002). CONCLUSION: Our results suggest that fasting insulin levels might be a predictor of the risk of hypoglycemia in people with T2D on treatment with SUs.

Patients' and Clinicians' Preferences on Outcomes and Medication Attributes for Type 2 Diabetes: a Mixed-Methods Study.

BACKGROUND: Patients' views on the relative importance of treatment outcomes and medication attributes for type 2 diabetes may differ from clinicians' perceptions. OBJECTIVE: To assess which treatment outcomes and medication attributes are considered important by patients and clinicians for therapeutic decisions in type 2 diabetes. DESIGN: Exploratory, sequential, mixed-methods design comprising a qualitative (focus groups) and a quantitative (survey) phase. PARTICIPANTS: Patients in the focus groups (n = 33) and the survey study (n = 656) were recruited from 4 and 9 diabetes clinics across Greece, respectively. Clinicians in the survey study (n = 363) were identified from Greek registries for healthcare professionals. MEASUREMENTS: We conducted 6 focus groups to obtain patients' views regarding the impact of type 2 diabetes on their lives. Identified themes informed the development of a survey, which aimed to assess which outcomes and medication attributes are considered most important by patients and clinicians. We calculated odds ratios to compare patients' and clinicians' responses. RESULTS: The focus groups identified 6 main themes and 15 subthemes. In the survey study, patients were more likely than clinicians to rate prevention of amputation (odds ratio, 9.32; 95% CI, 6.51 to 13.35), diabetic eye disease (6.16; 4.63 to 8.21), sexual dysfunction, and stroke as important, while clinicians were more likely than patients to choose risk for hypoglycemia, and reduction of all-cause mortality, HbA1c, and body weight. Compared with clinicians, patients were less concerned about drug cost (0.16; 0.11 to 0.23), but more concerned about route of administration and need for less frequent glucose self-monitoring. CONCLUSIONS: Patients and clinicians differ in the perception of the relative importance of treatment outcomes and drug characteristics. Individual patient preferences should be explored and implemented in the therapeutic decision-making for type 2 diabetes.

Influence of Supervised Disease Understanding and Diabetes Self-Management on Adherence to Oral Glucose-Lowering Treatment in Patients with Type 2 Diabetes.

INTRODUCTION: Systematic patient education has been reported to improve adherence to treatment, leading to better clinical outcomes. This cluster randomized real-world study investigated the effect of a systematic education program and telephone support on self-reported adherence to oral glucose-lowering treatment in patients with type 2 diabetes mellitus (T2DM). METHODS: Centers were randomized (1:1) to provide either standard-of-care (control group) or standard-of-care along with the education program and telephone support (empowerment group). Adherence to treatment and satisfaction with treatment were assessed using the four-item Morisky Medication Adherence Scale (MMAS-4) and the Diabetes Treatment Satisfaction Questionnaire (DTSQ). The study population included 457 patients (258/199 male/female) with T2DM and non-optimal glycemic control, on oral antidiabetic treatment (age 62.7 [11.4]; disease duration 8.5 [6.5] years). RESULTS: MMAS-4 high adherence rates for the control and empowerment groups were increased by 3.8% and 16.8% at 4 months (Breslow-Day test p = 0.04) and by 8.5% and 18.8% at 8 months of follow-up, respectively (Breslow-Day test p = 0.09), compared to baseline. Intense physical activity was increased in both control and empowerment groups by 2.3% and 13.9% at 4 months (Breslow-Day test p = 0.082) and by 4.0% and 22.5% at 8 months of follow-up (Breslow-Day test p < 0.001). Baseline mean (SD) HbA1c was significantly lower in the control group compared with the empowerment group [7.7% versus 8.0%, p = 0.001] and decreased in both groups at 4 months by 0.7% and 0.9%, respectively. The change from baseline in the mean DTSQ status score at 4 months was greater in the empowerment group, and the effect was sustained at 8 months (control group: 29.1, 30.5, and 30.9; empowerment group: 25.0, 28.7, and 29.4 at baseline, 4 and 8 months, respectively, p < 0.001). CONCLUSION: Systematic education combined with telephone support delivered by physicians might be associated with improvement in treatment adherence and treatment satisfaction in patients with T2DM. FUNDING: MSD, Greece.

Effect of liraglutide on ambulatory blood pressure in patients with hypertension and type 2 diabetes: A randomized, double-blind, placebo-controlled trial.

AIMS: To assess the effect of liraglutide on 24-hour ambulatory blood pressure and heart rate in patients with hypertension (pre- and stage 1 hypertension) and inadequately controlled Type 2 diabetes (glycated haemoglobin 7%-10% [53-86 mmol/mol]). MATERIALS AND METHODS: Eligible patients for this investigator-initiated, parallel-group, randomized, double-blind trial were on stable background antihyperglycaemic therapy excluding insulin, glucagon-like peptide-1 receptor agonists and dipeptidyl-peptidase-4 inhibitors. Participants were centrally randomized in a 1:1 ratio to daily liraglutide 0.6 mg, titrated to 1.2 mg after the first week, or placebo for 5 weeks. The primary outcome was change in 24-hour ambulatory systolic blood pressure (SBP), and secondary outcomes included change in ambulatory diastolic blood pressure (DBP) and heart rate. We also assessed renal sodium handling. RESULTS: Of 87 patients assessed for eligibility, 62 (66.1% men) with a mean age of 60.2 years were randomized to liraglutide (n = 31) or placebo (n = 31). All participants received background therapy with metformin, whilst 35.5% were treated concomitantly with sulphonylureas and 14.5% with pioglitazone. Compared with placebo, liraglutide reduced 24-hour SBP by -5.73 mm Hg (95% confidence interval [CI] -9.81 to -1.65) and had a neutral effect on 24-hour DBP (mean difference - 1.42 mm Hg; 95% CI -4.25 to 1.40), whilst increasing 24-hour heart rate by 6.16 beats/min (95% CI 3.25 to 9.07). Findings were consistent for daytime and night-time measurements. Liraglutide did not increase urine sodium excretion. CONCLUSION: Based on 24-hour ambulatory measurements, short-term treatment with liraglutide had a favourable effect on SBP whilst increasing heart rate.

Streptococcus thoraltensis Bacteremia: First Described Case as a Fever of Unknown Origin in Human.

Streptococcus thoraltensis has mainly been reported to cause infections in animals. Its clinical significance as a human pathogen has not yet been fully elucidated and needs further investigation. We describe here a case of bacteremia attributed to S. thoraltensis in a 55-year-old female patient admitted to our department due to fever of unknown origin. To the best of our knowledge, this is the first reported case of S. thoraltensis bacteremia in a human and the first reported case of S. thoraltensis as a cause of fever of unknown origin in human.