Effect of pioglitazone on inflammatory response and clinical outcome in T2DM patients with COVID-19: a randomized multicenter double-blind clinical trial.

Background: Coronavirus disease 2019 (COVID-19) caused by the coronavirus SARS-CoV-2, has emerged as a rapidly spreading contagious disease across the globe. Recent studies showed that people with diabetes mellitus, severe obesity, and cardiovascular disease are at higher risk of mortality from COVID-19. It has been suggested that the increased risk is due to the chronic inflammatory state associated with type 2 diabetes. This study aimed to evaluate the efficacy of pioglitazone, a strong insulin sensitizer with anti-inflammatory properties, in improving the clinical outcomes of patients with type 2 diabetes admitted with moderate-severe COVID-19. Method: We enrolled 350 patients with type 2 diabetes who were admitted to hospitals in Qatar and Kuwait with COVID-19. Patients were randomized to receive, in a double-blind fashion, pioglitazone (n = 189) or a matching placebo (n = 161) for 28 days. The study had two primary outcomes: (1) the incidence of a composite outcome composed of (a) the requirement for mechanical ventilation, (b) death, and (c) myocardial damage; and (2) an increase in C-reactive protein (CRP) levels. Results: The first primary outcome occurred in 28 participants (8%), and the secondary outcome occurred in 17. Treatment with pioglitazone showed a significant reduction in interleukin (IL)-3 levels compared with placebo treatment (mean (SD) 2.73 (± 2.14) [95% CI: 0.02, 1.1], p = 0.043 vs. 2.28 (± 1.67) [95% CI: - 0.23, 0.86], p = 0.3, respectively), with no effect seen in the levels of other inflammatory markers. Even though not significant, a few of the patients on pioglitazone exhibited serum troponin levels > 3 times higher than the normal range seen in patients on placebo. On the other hand, more patients on pioglitazone were admitted to the ICU than those with placebo, and no significant difference in the CRP reduction was observed between the two groups. Conclusion: The results of the present study demonstrate that pioglitazone treatment did not independently provide any additional clinical benefit to patients with type 2 diabetes admitted with a COVID-19 infection. Clinical trial registration: https://clinicaltrials.gov, identifier NCT04604223.

Health-related quality of life of Kuwaiti adults living with diabetes.

Diabetes is known to compromise patients' health-related quality of life (HRQoL). It is important to understand the HRQoL of Kuwaiti nationals living with diabetes and identify factors that negatively affect it. This study included 1,182 Kuwaiti nationals with diabetes, aged 18-80 years. Patients' demographic and HRQoL information was collected using the EuroQol EQ-5D-5L instrument. Mean values for each EQ-5D subscale were worst for mobility (1.9) and pain/discomfort (1.8). Most patients reported having no problems in self-care (84.4%). Older adults were most likely to report severe problems with mobility (p < 0.001). Females were more likely to report severe problems with anxiety and depression than males (p < 0.006). The EQ visual analog scale (EQ VAS), which reports perceived overall health on a 0-100 scale, showed a mean of 74.7 (±19.6). Patients with comorbidities and/or complications perceived their health to be worse, with VAS scores significantly lower (p < 0.001). Other factors that negatively affected VAS scores were being female, obesity, insulin usage, and lower levels of education. In conclusion, patients with diabetes who have comorbidities and/or complications perceived their health to be worse. Further research is required to evaluate if current diabetes management interventions help improve patients' HRQoL.

Utilization and cost of drugs for diabetes and its comorbidities and complications in Kuwait.

BACKGROUND: Diabetes imposes a large burden on countries' healthcare expenditures. In Kuwait, diabetes prevalence in adults is estimated at 22.0%%-double the worldwide prevalence (9.3%). There is little current data on pharmaceutical costs in Kuwait of managing diabetes and diabetes-related complications and comorbidities. OBJECTIVES: Estimate the utilization and cost of drugs for diabetes and diabetes-related complications and comorbidities in Kuwait for year 2018, as well determinants of costs. METHODS: This cross-sectional study used a multi-stage stratified sampling method. Patients were Kuwaiti citizens with diabetes, aged 18-80, recruited from all six governorates. Physicians collected demographic data, clinical data, and current drug prescription for each patient which was extrapolated for the full year of 2018. A prevalence-based approach and bottom-up costing were used. Data were described according to facility type (primary care vs. hospital). A generalized linear model with log function and normal distribution compared drug costs for patients with and without comorbidities/complications after adjustments for demographic and health confounders (gender, age group, disease duration, and obesity). RESULTS: Of 1182 diabetes patients, 64.0% had dyslipidemia and 57.7% had hypertension. Additionally, 40.7% had diabetes-related complications, most commonly neuropathy (19.7%). Of all diabetes patients, 85.9% used oral antidiabetics (alone or in combinations), 49.5% used insulin alone or in combinations, and 29.3% used both oral antidiabetics and insulin. The most frequently used oral drug was metformin (75.7%), followed by DPP4 inhibitors (40.2%) and SGLT2 inhibitors (23.8%). The most frequently used injectables were insulin glargine (36.6%), followed by GLP-1 receptor agonists (15.4%). Total annual drug cost for Kuwait's diabetic population for year 2018 was US$201 million (US$1,236.30 per patient for antidiabetics plus drugs for comorbidities/complications). CONCLUSIONS: Drug costs for treating diabetes and comorbidities/complications accounted for an estimated 22.8% of Kuwait's 2018 drug expenditures. Comorbidities and complications add 44.7% to the average drug cost per diabetes patient.

Sulfonylureas in the Current Practice of Type 2 Diabetes Management: Are They All the Same? Consensus from the Gulf Cooperation Council (GCC) Countries Advisory Board on Sulfonylureas.

Since their inception in the commercial market in the mid-twentieth century, sulfonylureas (SUs) have remained a therapeutic option in the management of type 2 diabetes (T2D). Despite their established glucose-lowering effects, there is no consensus among global experts and modern guidelines regarding the priority of SUs in relation to other therapeutic options, given the lack of evidence that SUs are associated with a low risk of macrovascular events and excess mortality. However, findings from recent trials and real-time observations have resolved this contentious issue somewhat, albeit to varying degrees. The present consensus discusses the role of SUs in contemporary diabetes management in the Gulf Cooperation Council (GCC) countries. Regional experts from these countries gathered virtually to formulate a consensus following presentations of topics relevant to SU therapy with an emphasis on gliclazide, including long-term efficacy, cost, end-organ benefits, and side effects, based on up-to-date evidence. The present narrative review reflects the conclusions of this assembly and provides a platform upon which future guidelines for the use of SUs in the GCC can be tailored.

Descriptive Regional Subanalysis of a Real-World Study in Patients with Type 2 Diabetes Treated with Gliclazide MR During Fasting: DIA-RAMADAN.

INTRODUCTION: To analyse the safety and effectiveness of gliclazide modified release (MR) in adults with type 2 diabetes mellitus participating in Ramadan from three geographically and culturally different regions of the world included in the DIA-RAMADAN study. METHODS: DIA-RAMADAN was a real-world, observational, international, non-comparative study. The global study population was divided into three regional subgroups, with data gathered at inclusion 6-8 weeks prior to Ramadan (V0), during Ramadan (4.5 weeks) and 4-6 weeks after Ramadan (V1). Primary endpoint was the proportion of patients reporting ≥ 1 symptomatic hypoglycaemic events (HE), which were collected using a patient diary along with other adverse events. RESULTS: Patient numbers from the three regions were n = 564 (46.5%; Indian sub-continent), n = 354 (29.1%; Middle East) and n = 296 (24.4%; South-East Asia). Patient baseline characteristics, demographics, fasting habits and antidiabetic treatments varied between regions. There were similar proportions of symptomatic HE between regions, with no severe HE. Significant weight reductions were observed in all regions following Ramadan, along with reductions in HbA1c and fasting plasma glucose. CONCLUSION: These real-world study data indicate that gliclazide MR is safe and effective for management of type 2 diabetes during Ramadan in all three regions studied as part of DIA-RAMADAN. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT04132934. INFOGRAPHIC.

A real-world study in patients with type 2 diabetes mellitus treated with gliclazide modified-release during fasting: DIA-RAMADAN.

AIMS: To explore the real-world safety and effectiveness of gliclazide modified release (MR) in patients with type 2 diabetes mellitus (T2DM) fasting during Ramadan. METHODS: DIA-RAMADAN (NCT04132934) was a prospective, international, observational study conducted in nine countries. Patients >18 years of age with T2DM (N = 1244) were examined at an inclusion visit (V0) occurring 6-8 weeks before the start of Ramadan. Patients received a diary to report treatment changes, hypoglycaemic events (HEs), and other adverse events. Gliclazide MR was taken once daily for 14-18 weeks. A second visit (V1) was conducted 4-6 weeks after the end of Ramadan. The primary endpoint was the proportion of patients reporting ≥1 symptomatic HE. Changes in HbA1c, fasting plasma glucose (FPG), and body weight were secondary endpoints. RESULTS: The proportion of patients reporting ≥1 symptomatic HE during Ramadan was low (2.2%) with no reported severe HEs. There was a significant reduction in HbA1c (-0.3%), FPG (-9.7 mg/dL), body weight (-0.5 kg) and body mass index (-0.2 kg/m2) between V0 and V1 (p < 0.001). CONCLUSIONS: Patients with T2DM treated with gliclazide MR during Ramadan have a low risk of hypoglycaemia and maintain glycaemic control and weight while fasting.

Diagnosis and management of osteoporosis in postmenopausal women in Gulf Cooperation Council (GCC) countries: consensus statement of the GCC countries' osteoporosis societies under the auspices of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO).

A consensus platform is provided by the experts of the Gulf Cooperation Council (GCC) countries' respective osteoporosis societies, on which specific guidelines can be developed further for regional use on the assessment and treatment of postmenopausal women at risk from fractures due to osteoporosis. INTRODUCTION: Guidance is provided in a Gulf Cooperation Council (GCC) country setting on the assessment and treatment of postmenopausal women at risk from fractures due to osteoporosis, which is an adaptation of the European guidance by Kanis et al., jointly published by the International Osteoporosis Foundation and the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). The respective osteoporosis societies of the Gulf Cooperation Council (GCC) countries assembled for a unifying consensus on the diagnosis and management of osteoporosis in postmenopausal women for the region. METHODS: The Chair for Biomarkers of Chronic Diseases (CBCD) in King Saud University (KSU), Riyadh, Kingdom of Saudi Arabia (KSA), in cooperation with the Saudi Osteoporosis Society (SOS), hosted regional experts and respective leaders from different GCC osteoporosis societies, together with an adviser from the ESCEO. An assembly of experts representing the different osteoporosis societies from Saudi Arabia, the UAE, Bahrain, Oman, and Kuwait gathered on February 15-16, 2019 in Riyadh, KSA for the formulation of a general osteoporosis consensus for the region. RESULTS: The following areas were covered: diagnosis of osteoporosis and assessment of fracture risk; general and pharmacological management of osteoporosis; and hip fractures, vitamin D, recommendation on which FRAX tool to follow, and the importance of country-specific FRAX® and fracture liaison services for secondary fracture prevention. CONCLUSIONS: A platform is provided on which specific guidelines can be developed for regional use in GCC.

Insulin Autoimmune Syndrome in a 25-Year-Old, Previously Healthy Kuwaiti Man.

Insulin autoimmune syndrome (IAS) is a disease characterized by hyperinsulinaemic hypoglycaemia associated with autoantibodies against endogenous insulin. We have described a case of a 25-year-old, previously healthy Kuwaiti man who was admitted to the Mubarak Al-Kabeer hospital with a history of recurrent hypoglycaemia. The patient revealed that he had taken several different injectable anabolic steroids and growth hormone with oral amino acids and other tablets (fat burners) for bodybuilding in the last two months. He denied knowingly using insulin or insulin analogues. The patient had elevated fasting insulin level (>301 uIU/mL) and elevated insulin autoantibodies (>100.0 IU/mL). After appropriate work-up, he was diagnosed with IAS. After treatment with prednisolone (1 mg/kg/day), the patient had complete recovery. In patients with repeated hypoglycaemia, IAS should be considered in the differential diagnosis. Glucocorticoid therapy can be effective for the treatment of hypoglycaemia in patients with IAS.

High HDL-C prevalence is common in type 1 diabetes and increases with age but is lower in Hispanic individuals.

High HDL-cholesterol (HDL-C) based on the 85th percentile of the 2009-2010 National Health and Education Survey (NHANES) was present in more than a third of 194 unselected subjects with type 1 diabetes (T1D). Age was associated with an increase and Hispanic ethnicity with a decrease in the prevalence of high HDL-C.