Polyagonists in Type 2 Diabetes Management.

PURPOSE OF THE REVIEW: This review summarizes the new developments in polyagonist pharmacotherapy for type 2 diabetes. RECENT FINDINGS: Several dual- and triple-agonists targeting different pathogenic pathways of type 2 diabetes have entered clinical trials and have led to significant improvements in glycaemia, body weight, fatty liver, and cardio-renal risk factors, with variable adverse event profiles but no new serious safety concerns. Combining agents with complementary and synergistic mechanisms of action have enhanced efficacy and safety. Targeting multiple pathogenic pathways simultaneously has led to enhanced benefits which potentially match those of bariatric surgery. Tirzepatide, cotadutide, BI456906, ritatrutide, and CagriSema have entered phase 3 clinical trials. Outcomes from published clinical studies are reviewed. Efficacy-safety profiles are heterogeneous between agents, suggesting the potential application of precision medicine and need for personalized approach in pharmacological management of type 2 diabetes and obesity. Polyagonism has become a key strategy to address the complex pathogenesis of type 2 diabetes and co-morbidities and increasing number of agents are moving through clinical trials. Heterogeneity in efficacy-safety profiles calls for application of precision medicine and need for judicious personalization of care.

Evaluation of the accuracy and precision of glucometers currently used in Sri Lanka.

AIMS: Life threatening macrovascular and microvascular complications of diabetes can be minimized by effective glycaemic control. Self monitoring of blood glucose with glucometers is recognized as a cost effective strategy to improve glycaemic control. However accuracy and precision of glucometers will determine the effectiveness of this strategy. We aimed to evaluate accuracy and precision of commonly used glucometers in Sri Lanka. MATERIALS AND METHODS: An observational study was conducted in a tertiary care setting including patients with diabetes and healthy volunteers. Eight commonly used glucometers were used. Blood glucose was measured in 50 participants (16 healthy volunteers, 34 patients with diabetes) in finger prick capillary blood using glucometers and venous blood using standard laboratory methods, and were compared to determine accuracy. Repeated measurements from same glucometer with a single finger prick were made and compared to determine precision. RESULTS: Only one glucometer showed insignificant difference to venous plasma glucose values. Only one glucometer met ADA recommended bias of <5%. None of the glucometers fell within the ISO recommendations for accuracy. CONCLUSION: Majority of commonly used glucometers in Sri Lanka do not meet the ADA recommendations and ISO standards for accuracy and precision. However their variations are unlikely to make significant adverse impact on patient management.

Plasma glucose in screening for diabetes and pre-diabetes: how much is too much? Analysis of fasting plasma glucose and oral glucose tolerance test in Sri Lankans.

BACKGROUND: Fasting plasma glucose (FPG) is the most commonly used screening tool for diabetes in Sri Lanka. Cut-off values from American Diabetes Association recommendations are adopted in the absence of local data. We aimed to establish FPG cut offs for Sri Lankans to screen for diabetes and pre-diabetes. METHODS: Data on FPG and diabetes/pre-diabetes status were obtained from Sri Lanka Diabetes and Cardiovascular Study (SLDCS), a community based island wide observational study conducted in 2005-6. Sensitivity specificity and area under the ROC curve were calculated for different FPG values. RESULTS: Study included 4014 community dwelling people after excluding people already on treatment for diabetes or pre-diabetes. Mean age was 45.3 (± 15) years and 60.4% were females. FPG cut off of 5.3 mmol/L showed better sensitivity and specificity than 5.6 mmol/L in detecting diabetes (87.8% and 84.4% Vs 80.8% and 92.1%) and pre-diabetes (54.7% and 87.0% Vs 43.8% and 94.2%). CONCLUSIONS: A lower FPG cut off of 5.3 mmol/L has a better sensitivity and acceptable specificity in screening for diabetes and pre-diabetes in Sri Lankan adults.

Hypoglycaemia in diabetes: do we think enough of the cause? An observational study on prevalence and causes of hypoglycaemia among patients with type 2 diabetes in an out-patient setting in Sri Lanka.

BACKGROUND: Hypoglycaemia is a feared experience for people with diabetes. We aimed to study the prevalence and causes of hypoglycaemia among Sri Lankans with diabetes. METHODS: One thousand patients with diabetes attending a private sector diabetic clinic were interviewed using a structured questionnaire. Hypoglycaemic episodes within the preceding month were inquired and severity was graded according to clinical features and/or capillary blood glucose levels. RESULTS: Mean age 55.0 years (± 12.5), 58.6% were males, mean diabetes duration 10.6 years (± 8.1), mean FPG 7.48 mmol/l (± 2.79) and mean HbA1c 7.82% (± 1.71) (62 mmol/mol). Of them, 26.1%. (mild 20.7%, moderate 3.9%, and severe 1.5%) experienced symptomatic hypoglycaemia. Sudden change diet (46.7%), unaccustomed exercise (15.7%) and increase in antihyperglycaemic therapy dosage (14.9%) were the recognized causes. Cause was not recognized by 16.3%. Non-prescribed native food items accounted for hypoglycaemia in 16.9% of patients (Momordica charantia 54.5%, Costus speciosus 52.3%, Salacia prinoides 11.4%, Coccinia grandis 6.8%, Adenanthera pavonina 4.5%). Severity of hypoglycaemia was positively correlated to age and duration of diabetes but not to HbA1C. CONCLUSION: Hypoglycaemia is common among patients with diabetes. Patients need advice on regular diet and exercise. Consumption of non-prescribed native foods should be considered as a possible cause.

Intra cavernous aneurysm of internal carotid artery masquerading as a pituitary adenoma: a case report.

BACKGROUND: Pituitary dysfunction in adults are often associated with tumors of the gland and manifests with mass effects and hypopituitarism. MRI of pituitary region often provides confirmation of the diagnosis and assists in planning neurosurgery. CASE PRESENTATION: A 69 years old female evaluated for chronic headache was found to have a supra-sellar mass lesion that mimicked a pituitary tumor, with biochemical evidence of hypopituitarism. Cerebral angiogram confirmed the diagnosis of an aneurysm of the intracavernous internal carotid artery. She was successfully treated with coil embolization of the aneurysm and achieved resolution of symptoms and return of biochemistries to normal. CONCLUSION: Carotid aneurysm can mimc pituitary tumours clinically and radiologically on MRI scan. This rare possibility should be considered in evaluating supra-sellar masses to avoid catastrophic consequences.