Oral Antihyperglycemic Agents Research Articles

Glucagon-Like Peptide-1 Receptor Agonists are Not Associated with an Increased Risk of Progressing to Vision-Threatening Diabetic Retinopathy

ABSTRACT Purpose Glucagon-like peptide-1 receptor agonists (GLP-1RA) are used to treat type 2 diabetes mellitus (DM) by augmenting insulin release and sensitivity. We assessed the overall risk for development of vision-threatening diabetic retinopathy (VTDR), proliferative diabetic retinopathy (PDR), and diabetic macular edema (DME), among GLP-1RA users. Methods A retrospective cohort of patients with NPDR newly started on a GLP-1RA from a national insurance claims database was compared to a cohort of patients treated with other oral anti-diabetic agents and matched for age, sex, race, index year, and number of active diabetic medications. Exclusions occurred for < 2 years in the database before diagnosis; prior diagnoses of PDR, DME, vitreous hemorrhage, and/or other retinal vascular diseases; and prior intraocular treatment for VTDR. Results A total of 6093 users of GLP-1RA were matched to 14,122 controls. In the GLP-1RA cohort, 632 (10.1%), 76 (1.2%), and 544 (8.9%) patients progressed to VTDR, PDR, or DME, respectively. This is compared to 1332 (9.5%) VTDR, 165 (1.2%) PDR, or 1148 (8.1%) DME in the control group. Accounting for underlying DM severity with IPTW, no difference in hazard was seen in the GLP-1RA cohort compared to controls for progression to VTDR (HR = 1.02, 95%CI: 0.92–1.14 p = 0.69), DME (HR = 1.06, 95%CI: 0.95–1.1.9, p = 0.31), or PDR (HR = 0.81, 95%CI: 0.58–1.12, p = 0.20). Conclusion We found no difference in the risk for vision-threatening diabetic retinopathy, nor for its component diseases, DME or PDR, with GLP-1RA use compared to other oral anti-hyperglycemic agents in patients with NPDR.

Metformin suppresses gastric cancer progression by disrupting the STAT1-PRMT1 axis

Gastric cancer (GC) is a common form of cancer and the leading cause of cancer-related deaths worldwide. Chemotherapy is the primary treatment for patients with unresectable or partially resectable GC. However, its adverse effects and chemoresistance greatly restrict its applicability and efficacy. Although HER2-targeted therapy and immunotherapy have been successfully used for GC treatment, their beneficial population is limited. To expand the range of cancer treatments, drug repurposing has emerged as a promising strategy. In this study, we evaluated the potential of Metformin, an oral anti-hyperglycemic agent, to suppress GC progression both in vivo and in vitro. Functional investigations showed that Metformin significantly inhibits GC proliferation and migration. Furthermore, we discovered that Metformin bound and disrupted STAT1 phosphorylation, inhibiting PRMT1 expression and consequently GC progression. In conclusion, our study not only provides further evidence for the anti-GC role of Metformin but also identifies the direct target mediating the tumor-inhibitory effects of Metformin in GC.

Effectiveness, Simplification and Persistence of IDegLira in Poorly Controlled People with Type 2 Diabetes: A 4-Year Follow-Up Real-World Study.

Efficacy and safety of the fixed ratio combination of insulin degludec and liraglutide (IDegLira) has been largely documented. However, long-term data are limited. This study aimed at describing persistence in therapy and the effectiveness at 48months of IDegLira. We conducted an observational study based on retrospective chart review. All patients treated with IDegLira during 2018-2022 were included. Data on treatment approaches and clinical outcomes were collected at the first prescription of IDegLira (T0) and after 6, 12, 24, 36, and 48months. Overall, 156 patients (mean age 68years, 64.1% men) started IDegLira, of whom 88 (56.4%) were previously treated with basal-oral therapy (BOT) and 68 (43.6%) with basal-bolus schemes (BB). Before starting IDegLira, 23.8% were treated with ≥ 2 oral antihyperglycemic agents in association with insulin; at T0, the proportion decreased to 3.2%. Short-acting insulin was discontinued after the first week. After 48months, levels of HbA1c were significantly reduced by 1.34% in the BOT group and 1.07% in the BB group (p < 0.0001 in both groups). In the BOT group, FBG levels decreased by about 50mg/dl and body weight was unchanged. In the BB group, FBG levels decreased by about 40mg/dl and body weight was significantly reduced by an average of 7.7kg. Five patients (3.2%) interrupted therapy with IDegLira during 48months, and no severe hypoglycemia occurred. Our study emphasizes the important role of IDegLira in maintaining a good metabolic control while minimizing the risk of major hypoglycemia and weight gain in the long term. The substantial simplification of treatment schemes can increase adherence.

Efficacy of Different Treatment Approaches (Insulin and Metformin) in Women with Gestational Diabetes Mellitus (GDM)

Background and Purpose: The pharmacotherapy options in patients with gestational diabetes mellitus (GDM) are insulin or oral antihyperglycemic agents. Insulin is the preferred medication for treating hyperglycemia, but in recent years, metformin has been increasingly used in the treatment of GDM. Aim: The aim is to assess the efficacy of different treatments (insulin and metformin) in women with GDM. Methods: Screening for GDM was performed in 2422 pregnant women and revealed GDM in 119 women [75 g oral glucose tolerance test (OGTT) was performed at 24–28 weeks of gestation]. All patients started treatment at 24–29 weeks of gestation. The patients were divided into two groups (Gr.): Gr. 1 had 68 patients treated with diet and insulin therapy. Gr. 2 had 51 patients treated with diet and metformin. Results: In the 2nd trimester, HbA1c (%) levels for Gr. 1 and Gr. 2 were 6.7 (0.05) and 6.4 (0.6), respectively. By term, HbA1c levels statistically decreased in both groups, but we did not find a statistical difference between the groups. Women from Gr. 2 gained less weight compared to Gr. 1 (1.89 ± 3.88 vs. 4.53 ± 3.67 kg; P = 0.003). In Gr. 1, the percentage of preeclampsia was 2.9%, and in Gr. 2, 3.9% (P = 0.7773, OR – 1.33). We did not find a statistical difference between the groups. The incidence of preterm delivery before 37 weeks of gestation in Gr. 1 was lower than in Gr. 2 (P = 0.7311, OR – 1.33), and we also did not find a statistical difference between the groups. Perinatal mortality was observed in Gr. 1 – 1.4% and in Gr. 2 – 1.9% (P = 0.8402, OR – 1.33). In both groups, we observed a high percentage of cesarean section (Gr. 1 – 32.3% and Gr. 2 – 29.4% (P = 0.7651, OR -1.0909), but we did not find a statistical difference between the groups. In both groups, the percentage of macrosomia was high, despite good glycemic control maintained through pregnancies: 20.0% and 23.0% for Gr. 1 and Gr. 2, respectively (P = 0.9236, OR – 1.0256), and again no statistical difference was found between the groups. Percent of neonatal hypoglycemia was lower in Gr. 2 (1.9%) than in Gr. 1 (4.41%) (P = 0.9236, OR – 1.0256). Percent of respiratory distress syndrome was 2.94% and 3.92% for Gr. 1 and Gr. 2, respectively (P = 0.9694, OR – 0.9893), with no statistical difference between the groups. Conclusion: We did not find differences between patients treated with diet and insulin therapy and patients treated with diet and metformin. The percentage of preeclampsia, preterm delivery, macrosomia, and perinatal death were similar in both groups; only maternal weight gain was lower in the metformin group.

Vascular contraction of umbilical arteries of pregnant women with preeclampsia.

Potassium channels have an important role in the vascular adaptation during pregnancy and a reduction in the expression of adenosine triphosphate-sensitive potassium channels (Katp) has been linked to preeclampsia. Activation of Katp induces vasodilation; however, no previous study has been conducted to evaluate the effects of the inhibition of these channels in the contractility of preeclamptic arteries. Glibenclamide is an oral antihyperglycemic agent that inhibits Katp and has been widely used in vascular studies. To investigate the effects of the inhibition of Katp, umbilical arteries of preeclamptic women and women with healthy pregnancies were assessed by vascular contractility experiments, in the presence or absence of glibenclamide. The umbilical arteries were challenged with cumulative concentrations of potassium chloride (KCl) and serotonin. There were no differences between the groups concerning the maternal age and gestational age of the patients. The percentage of smokers, caucasians and primiparae per group was also similar. On the other hand, blood pressure parameters were elevated in the preeclamptic group. In addition, the preeclamptic group presented a significantly higher body mass index. The newborns of both groups presented similar APGAR scores and weights. In the presence of glibenclamide, there was an increase in the KCl-induced contractions only in vessels from the PE group, showing a possible involvement of these channels in the disorder.

Gliptins and acute pancreatitis in patients with type 2 diabetes: a review

Diabetes mellitus is a chronic, metabolic, and complex disease that requires continuous treatment and medical care. Type 2 diabetes (T2DM) is disinfected by dysfunction of beta cells and insulin resistance. Gliptins are oral anti-hyperglycemic agents that control hyperglycemia. Acute pancreatitis (AP) is an acute inflammation that occurs in the pancreas. The correlation between acute pancreatitis and diabetes is complex, and there are many incorporated factors, such as anti-hyperglycemic drugs. The oresnt review aimed at providing an overview of acute pancreatitis and its association with T2DM, gliptins as a treatment for T2DM, and the correlation between AP and gliptins among T2DM patients. Scientific databases were used for searching for articles related to our subject. A variety of keywords were used for the search purpose, including &amp;quot;T2DM, AP, Association, Correlation, Incidence, Prevalence, Gliptin, dipeptidyl-peptidase-4 inhibitors.&amp;quot; Articles of relevance included those written in the English language, of any type, and conducted on the current subject. To cover as much of the current topic as possible, the discussion of the review contained three major sections. The first section covered acute pancreatitis and its connection to T2DM. In the second section, gliptin agents, safety, and negative effects were discussed. The third section discussed the correlation between acute pancreatitis and gliptin in T2DM patients. Acute pancreatitis was highly developed among type 2 diabetic patients; however, the correlation between acute pancreatitis and gliptins is controversial.

Metformin: An Oral Anti-Hyperglycaemic Agent for the Treatment of Type 2 Diabetes

Metformin is one of the safest and most effective first-line glucose-lowering oral drug therapies for overweight and obese type 2 diabetes (T2D) patients, and those with normal kidney function. It is one of the drugs of Biguanide class of anti-diabetic compounds. It prevents the production of hepatic glucose, increases fatty acid oxidation, enhances insulin sensitivity, decreases lipid synthesis, and impedes gluconeogenesis. Sometimes it is used in combination with insulin or other oral medications. It should be used very carefully who have surgery, trauma, heart failure, severe kidney disease, and impaired liver functions. Some patients face side effects of Metformin and they should take it considering possible side effects of it. In this study aspect of Metformin is discussed as a guideline for the proper treatment T2D patients.

THU360 Hyperglycemic DKA In Patient On Monotherapy With SGLT-2 Inhibitor

Abstract Disclosure: S. Ahmed: None. L. Medina Mora: None. A. Sanchez Ruiz: None. L. Poretsky: None. Background: SGLT2 inhibitors have a rare but increasingly reported risk of euglycemic diabetic ketoacidosis. Hyperglycemic diabetic ketoacidosis is not an expected risk of SGLT-2 inhibitors. Clinical Case: 52-year-old male with history of type 2 Diabetes presented with progressive weakness, shortness of breath, nausea and vomiting worsening over 48 hours. He reported increased polydipsia and polyuria. Patient was found to have a blood glucose of 685 mg/dL associated with an anion gap of 28 mm/L and bicarbonate level of 6 mm/L. Beta hydroxybutyrate level was &amp;gt;8.0 mmoL/L. He was diagnosed with hyperglycemic diabetic ketoacidosis, given intravenous isotonic fluid and started on an insulin drip. The anion gap closed and he was successfully transitioned off the insulin drip to a basal bolus regimen of insulin. The patient improved quickly without any complication. The patient was never on insulin therapy prior to admission. No obvious source of infection was discovered to precipitate the event. The patient had a 7-year history of diabetes and was only managed on oral medications at home. He was previously on Janumet 50-1000mg twice a day and changed to only dapagliflozin 10mg 9 months prior to the current episode. He never experienced ketoacidosis or hyperosmolar hyperglycemic state. Hemoglobin A1c was found to be 8.0%. He reported that his A1c levels were always less than 8%. Autoimmune workup for type 1 Diabetes was done. C-peptide level was found to be 1.5ng/mL. Patient appeared to have an adequate insulin level despite the recent event of diabetic ketoacidosis. Patient was discharged on 10 units of Glargine® at bedtime and 3 units of Lispro® before meals. He was given glucometer teaching with an appointment for endocrine follow up. During follow up Glutamic Acid decarboxylase, Islet cell, Insulin and Zinc 8 transporter antibodies have come back negative. Patient is being planned for transition to oral antihyperglycemic agents which will not include an SGLT2 inhibitor. A MODY panel is pending results for further evaluation. Conclusion: Monotherapy of SGLT-2 inhibitors appears to not only have a risk of euglycemic diabetic ketoacidosis but also a risk of hyperglycemic diabetic ketoacidosis in type 2 diabetics. In this case we presented a case of hyperglycemic diabetic ketoacidosis in a type 2 diabetic on therapy with dapagliflozin. Presentation: Thursday, June 15, 2023

AN ANALYTICAL REVIEW-BASED STUDY ON SITAGLIPTIN

Sitagliptin is an oral anti-hyperglycemic agent of the dipeptidyl peptidase-4 (DPP-4) inhibitor magnificence used inside the remedy of type-2 diabetes. It stimulates insulin release and reduces glucagon levels by inhibiting of inactivation of the incretin in a glucose-dependent manner. In 2013 it was the second best- selling drug in the U.S. This evaluation encompasses diverse analytical strategies inclusive of spectrometry, high-overall performance liquid chromatography (HPLC), liquid chromatography-electrospray ionization- mass spectrometry (LC-ESI-MS-MS), liquid chromatography-mass spectrometry (LC-MS), capillary electrophoresis (CE), ultra-overall performance liquid chromatography (UPLC), high-overall performance skinny layer chromatography (HPTLC) and fuel line chromatography-mass spectrometry (GC-MS) for the estimation of sitagliptin in unmarried and/or in combination. Keywords: Sitagliptin, Analytical methods, Type-2 diabetes.

Metformin targets intestinal immune system signaling pathways in a high-fat diet-induced mouse model of obesity and insulin resistance.

Research findings of the past decade have highlighted the gut as the main site of action of the oral antihyperglycemic agent metformin despite its pharmacological role in the liver. Extensive evidence supports metformin's modulatory effect on the composition and function of gut microbiota, nevertheless, the underlying mechanisms of the host responses remain elusive. Our study aimed to evaluate metformin-induced alterations in the intestinal transcriptome profiles at different metabolic states. The high-fat diet-induced mouse model of obesity and insulin resistance of both sexes was developed in a randomized block experiment and bulk RNA-Seq of the ileum tissue was the method of choice for comparative transcriptional profiling after metformin intervention for ten weeks. We found a prominent transcriptional effect of the diet itself with comparatively fewer genes responding to metformin intervention. The overrepresentation of immune-related genes was observed, including pronounced metformin-induced upregulation of immunoglobulin heavy-chain variable region coding Ighv1-7 gene in both high-fat diet and control diet-fed animals. Moreover, we provide evidence of the downregulation NF-kappa B signaling pathway in the small intestine of both obese and insulin-resistant animals as well as control animals after metformin treatment. Finally, our data pinpoint the gut microbiota as a crucial component in the metformin-mediated downregulation of NF-kappa B signaling evidenced by a positive correlation between the Rel and Rela gene expression levels and abundances of Parabacteroides distasonis, Bacteroides spp., and Lactobacillus spp. in the gut microbiota of the same animals. Our study supports the immunomodulatory effect of metformin in the ileum of obese and insulin-resistant C57BL/6N mice contributed by intestinal immunoglobulin responses, with a prominent emphasis on the downregulation of NF-kappa B signaling pathway, associated with alterations in the composition of the gut microbiome.

Evaluation of the safety of inpatient empagliflozin in a real-world setting

Background Empagliflozin is a sodium glucose co-transporter 2 (SGLT2) inhibitor recommended by the American Diabetes Association for outpatient use. Support for its inpatient role is not well established due to possible safety concerns. Methods This was a retrospective study at an academic medical center between January 1, 2021, and December 31, 2021, evaluating the safety and efficacy of empagliflozin compared to other oral antihyperglycemic agents. Patients with established heart failure with or without diabetes were included if they received at least one dose of oral antihyperglycemic agent with 48 hours of fingerstick blood glucose checks during the hospitalization. A total of 227 patients were included. The primary endpoint was a composite of adverse events including urinary tract infection, acute kidney injury, diabetic ketoacidosis, renal replacement therapy, and necrotizing fasciitis. Additional endpoints included daily insulin requirements, hypoglycemia, and hypotension. Results Rates of composite adverse events were similar between the empagliflozin group and other oral antihyperglycemic agents (19.3% vs. 12.6% respectively, P = 0.17). There were no instances of renal replacement therapy, diabetic ketoacidosis, or necrotizing fasciitis. The secondary endpoint of basal insulin requirements showed no differences between the two groups. In the empagliflozin cohort, more patients experienced hypotension (23.4% vs. 7.8%; P < 0.01). Conclusion This real-world study of empagliflozin use in the inpatient setting found no significant differences in safety endpoints between empagliflozin and other oral antihyperglycemic agents. Larger-scale studies need to be performed before the use of empagliflozin can be routinely recommended in the inpatient setting.

Efficacy, safety and tolerability of imeglimin inpatients with type 2 diabetes mellitus: Ameta-analysis of randomized controlled trials.

This meta-analysis aimed to evaluate the efficacy and safety/tolerability of imeglimin, a novel oral antihyperglycemic agent, administered as monotherapy and adjunctive therapy in patients with type 2 diabetes mellitus. Parallel-group randomized controlled trials comparing imeglimin with placebo in adults with type 2 diabetes mellitus were included. Risk ratios or weighted mean differences (WMD) and 95% confidence intervals (CIs) were calculated using random effects models. The primary outcome for efficacy was the change in glycated hemoglobin (HbA1c). Secondary outcomes included other efficacy-related outcomes, specific adverse events, and changes in body weight and lipid parameters. Nine randomized controlled trials (n = 1,655) were included. When analyzed by dose, there was a significant difference in glycated hemoglobin (%) between imeglimin monotherapy and placebo at doses >1,000 mg twice daily (1,000 mg: studies N = 3, patients n = 517, WMD = -0.714, P < 0.001; 1,500 mg: N = 5, n = 448, WMD = -0.531, P = 0.020; 2,000 mg: N = 1, n = 149, WMD = -0.450, P = 0.005). Imeglimin adjunctive therapy significantly improved glycated hemoglobin over placebo at doses of 1,000 mg (N = 1, n = 214, WMD = -0.600, P < 0.001) and 1,500 mg (N = 2, n = 324, WMD = -0.576, P < 0.001). Subgroup analysis of the primary outcome showed that imeglimin was effective regardless of chronic kidney disease category, with studies carried out in Japan and in patients with lower body mass index showing a trend toward improved imeglimin efficacy. There were no significant differences between imeglimin and placebo in the risk of all-cause discontinuation and the proportion of patients who presented with at least one adverse event. Imeglimin is efficacious, safe, and well tolerated as monotherapy and adjunctive therapy.

Evaluation of the Effect of Dapagliflozin on CRP Levels in Type 2 Diabetes Patients

Type 2 diabetes mellitus (T2DM) is an increasingly prevalent chronic disease that associates with an increased risk of micro-and macrovascular complications. There is persuasive evidence that dapagliflozin may reduce chronic inflammation besides its glucose-lowering effect, which in term prevents the development of the disease and its complications. Therefore, this study aims to evaluate the effects of dapagliflozin on the inflammatory marker C-reactive protein (CRP) levels in T2DM patients. Patients with T2DM were randomly assigned into two groups, group 1 (n=52) receiving a daily dose of dapagliflozin as an add-on therapy with oral antihyperglycemic agents, and group 2 (control, n=60) who received oral antihyperglycemic agents (Metformin, Sulfonylureas, Thiazolidinediones, and Gliptins). After six months, our results showed a significant change in CRP levels from baseline after receiving dapagliflozin compared to the control. Although the reduction level of CRP was statically significant with both 5 mg and 10 mg doses, it was higher with the latter one. In addition, the reduction in CRP levels was statistically significant in both controlled and uncontrolled, but more important in uncontrolled disease. An insignificant positive correlation was seen between HbA1c and CRP on admission (r: 0.21, p: 0.1) and during the follow-up period, at 3 months (r: 0.10, p: 0.4) and 6 months (r: 0.08, p: 0.5). Our study showed that dapagliflozin has a beneficial effect on inflammation by reducing CRP levels CRP in patients with T2DM.

Combined experimental/computational aspects for the molecular interaction of empagliflozin with bovine serum albumin: Quantification and application to human plasma.

Empagliflozin (EMP) is an oral antihyperglycemic agent for type 2 diabetic patients. The molecular binding of EMP to bovine serum albumin (BSA) was elucidated by a combined experimental/computational approach to fulfil the pharmacokinetics and pharmacodynamics gaps of the cited drug for further development. Fluorescence, synchronous, and three-dimensional fluorescence spectroscopy verified that EMP quenched BSA native fluorescence through a dual static/dynamic mechanism that was further supported by Fӧrster resonance energy transfer and ultraviolet absorption spectroscopy. Fourier transform infrared spectroscopy revealed the conformational variations in BSA secondary structure induced by EMP. Thermodynamic properties of the BSA-EMP complex were also investigated, and the hydrophobic interactions' role in the binding process was demonstrated by the computed enthalpy (ΔH =6.558 kJ mol-1 ) and entropy (ΔS = 69.333 J mol-1 K-1 ). Gibbs free energy (ΔG) values were negative at three distinct temperatures, illuminating the spontaneity of this interaction. In addition, molecular docking studies depicted the optimal fitting of EMP to BSA on Site I (sub-domain IIA) through three hydrogen bonds. Additionally, and based on the quenching effect of EMP on BSA fluorescence, this study suggests a simple validated spectrofluorometric method for the quantitation of the studied drug in bulk form and human plasma samples with reasonable recoveries (96.99-103.10%).

Type 2 diabetes with obesity and hypertension: prevalence and sociodemographic risk factors in Yemen

BACKGROUND: Diabetes Mellitus is a rapidly growing and challenging health issue of the 21st century. Type 2 diabetes (T2D) is a major risk factor for obesity and hypertension (HTN). The prevalence of HTN and obesity in T2D patients is not well documented in the country of Yemen. AIM: The focus of this study was to assess the prevalence of hypertension and obesity in patients with type 2 diabetes mellitus in Yemen.METHODS: A cross-sectional study was carried out in Dhamar city hospitals. Patients diagnosed with diabetes (300 males and females: 30 years old and/or above) visiting an endocrinology and diabetes clinic in Dhamar city hospital for the first time were examined and evaluated for blood glucose levels, mode of treatment, duration of the disorder and body mass index. Socio-demographic and clinical data were collected using pretested questionnaires. Ethical approval was obtained from corresponding ethical committees from Dhamar University and hospitals. Data were analyzed using SPSS 23 version.RESULTS: The prevalence of overweight and/or obesity in T2D was 60.67%, and hypertension was 35.66%. The occurrence of T2D was predominant in females (56.33%), patients with an age over 50 years (61%), and rural dwellers (74%). The mode of treatment was mainly through oral antihyperglycemic and hypoglycemic agents (79.3%). A large population (66.3%) showed poor control of blood glucose levels ranging from more than 131 to 500 mg/dL and the type of work these patients were involved in was mostly physically inactive (64%). The body mass index revealed that more than 35% were found to be overweight and 23% to be obese. Patients with hypertension and undergoing treatment for the same showed a significant (P &lt; 0.001) increase in blood glucose level compared to those who were not diagnosed with HTN.CONCLUSION: The prevalence of obesity, HTN, and poor glycemic control in patients with T2D is high, especially in females.

The Effectiveness of an App (Insulia) in Recommending Basal Insulin Doses for French Patients With Type 2 Diabetes Mellitus: Longitudinal Observational Study.

For patients with type 2 diabetes (T2D), calculating the daily dose of basal insulin may be challenging. Insulia is a digital remote monitoring solution that uses clinical algorithms to recommend basal insulin doses. A predecessor device was evaluated in the TeleDiab-2 randomized controlled trial, showing that a higher percentage of patients using the app achieved their target fasting blood glucose (FBG) level compared to the control group, and insulin doses were adjusted to higher levels without hypoglycemia. This study aims to analyze how the glycemic control of Insulia users has evolved when using the app in a real-life setting in France. A retrospective observational analysis of data collected through the device in adult French patients with T2D treated with basal insulin and oral antihyperglycemic agents using the system for ≥6 months was conducted. Analyses were descriptive and distinguished the results in a subpopulation of regular and compliant users of the app. Glycemic outcomes were estimated considering the percentage of patients who achieved their individualized FBG target between 5.5 and 6 months following the initiation of device use, the frequency of hypoglycemia resulting in a treatment change over the 6-month period of exposure, and the evolution of the average hemoglobin A1c (HbA1c) level over the same period. Of the 484 users, 373 (77.1%) performed at least one dose calculation. A total of 221 (59.2%) users were men. When app use started, the mean age, BMI, HbA1c, and basal insulin dose were 55.8 (SD 11.9) years, 30.6 (SD 5.9) kg/m2, 10.1% (SD 2.0%), and 25.5 (SD 15.8) IU/day, respectively. Over a median use duration of 5.0 (95% CI 3.8-5.7) months, patients used the system 5.8 (SD 1.6) times per week on average, and 73.4% of their injected doses were consistent with the app's suggested doses. Among regular and compliant user patients (n=91, ≥5 measurements/week and ≥80% adherence to calculated doses), 60% (55/91) achieved the FBG target (±5%) at 6 months (5.5-6 months) versus 51.5% (145/282) of the other patients (P=.15). There was an increase in the proportion of patients achieving their target FBG for regular and compliant users (+1.86% every 2 weeks) without clear improvement in other patients. A logistic model did not identify the variables that were significantly associated with this outcome among regular and compliant users. In the overall population, the incidence of reported hypoglycemia decreased simultaneously (-0.16%/month). Among 82 patients, the mean HbA1c decreased from 9.9% to 7.2% at 6 months. An improvement in glycemic control as measured by the percentage of patients reaching their FBG individualized target range without increasing hypoglycemic risk was observed in patients using the Insulia app, especially among regular users following the dose recommendations of the algorithm.

Patient perception towards shifting oral antihyperglycemic agents to injectable insulin and associated factors in the diabetes clinic of Tikur Anbessa specialized hospital: Cross-sectional study

BackgroundWith the growing understanding of the importance of preserving adequate glycemic control for the prevention of long-term diabetes-related complications, insulin therapy has become increasingly recommended for type 2 diabetes. However, insulin use in various healthcare settings remains low due to patients' low levels of acceptability of insulin therapy, which necessitates evaluating patients' attitudes. ObjectiveTo assess patients' perception toward shifting oral antihyperglycemic agents to insulin and associated factors at the ambulatory diabetes clinics of Tikur Anbessa Specialized Hospital (TASH). MethodA cross-sectional study design was applied using a pre-tested interviewer-administered questionnaire on adult type 2 diabetes patients on follow-up at the diabetes clinic of TASH, Ethiopia from July to September 2021. The questionnaire tool was adapted from Insulin Treatment Appraisal Scale with modifications to fit the purpose of the study. Data was gathered, cleaned up, entered, and analyzed using Statistical Package for the Social Sciences (SPSS) version 23 for descriptive and logistic regression. For logistic regression data, a p-value of 0.05 was used to determine the statistical significance. ResultOf 293 patients, 65.9% were female. Study participants had a mean age of 53.9 ± 10.9 years. About 45% and 75% of the participants have complications and comorbidities, respectively with a mean disease duration of 19.16 ± 8.2 years. Almost 54% of patients on oral antihyperglycemic agents were unwilling to start insulin. A perception score below the median was observed in 56.3% of the respondents. Patients with primary and secondary education were 45% and 42% less likely to have a poor perception of shifting oral antihyperglycemic agents to insulin than those who couldn't read or write (P < 0.05), respectively. The study found that participants who were taking only oral antihyperglycemic agents had a 2.76 times poor perception than those who are on insulin treatment (P < 0.001). ConclusionPoor perception toward shifting oral antihyperglycemic agents to insulin was found to be high among study participants. It was substantially correlated with low educational attainment, financial constraints, exclusively using oral antihyperglycemic agents, duration of disease, and absence of disease complications.

Efficacy of Liraglutide Versus Gliclazide in Treatment of Patients with Type II Diabetes Mellitus: Systematic Review and Meta-Analysis

BackgroundType 2 diabetes mellitus (T2DM) triggers long-lasting and progressive metabolic disorders, causing a severe health issue resulting in several high predominance and dangerous complications. Liraglutide is a glucagon-like peptide-1 (GLP-1), while gliclazide is an oral antihyperglycemic agent. ObjectivesTo measure the efficacy of gliclazide and liraglutide on T2DM patients. MethodsWe performed systematic reviews and meta-analyses by searching two databases, PubMed and Web of Science (WOS), for relevant studies published in the literature during May 2021. We included clinical trials and observational studies and extracted the patients' baseline characteristics and outcomes. We used the Cochrane Handbook of Systematic Reviews of Interventions and the Newcastle Ottawa scale to assess the included studies' quality. The statistical analysis was performed by STATA Version 16. ResultsOur meta-analysis included three studies (two clinical trials and one observational study) with 137 participants, 71 in the gliclazide and 66 in the liraglutide groups. Gliclazide had a non-significant reduction of glycated hemoglobin (HbA1c) compared to liraglutide (mean difference [MD] 0.53; 95% CI -0.01, 1.07; P = 0.06). Gliclazide had a non-significant decreasing of body weight compared to liraglutide (standardized mean difference [SMD] 0.32; 95% CI -0.02, 1.07; P = 0.06). Gliclazide had a non-significant decreasing of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) compared to liraglutide (SMD -0.11; 95% CI -0.45, 0.23; P = 0.53) and (MD -0.02; 95% CI -0.15, 0.10; P = 0.7). ConclusionsLiraglutide is more effective in reducing HbA1c, body weight LDL-C, and HDL-C than gliclazide.

SGLT-2 inhibitors in nephrotic-range proteinuria: emerging clinical evidence.

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are a class of novel oral anti-hyperglycemic agents which are increasingly used in clinical practice. SGLT-2 inhibitors improve glycemic control and cardiorenal outcomes, promote weight loss, and reduce blood pressure. Randomized controlled trials have demonstrated that SGLT-2 inhibitors reduce proteinuria and delay progression of kidney disease in patients with albuminuria. However, whether SGLT-2 inhibitors have similar benefits in patients with nephrotic-range proteinuria has not been well established. Evidence to date has been limited to case reports, case series and secondary analyses of randomized controlled trials. This is the first comprehensive review on the effectiveness of SGLT-2 inhibitors for the treatment of patients with nephrotic-range albuminuria or proteinuria. Overall findings support a likely beneficial role of SGLT-2 inhibitors in reducing proteinuria and delaying chronic kidney disease progression in patients with nephrotic-range proteinuria.

The Association between Adherence to Oral Antihyperglycemic Agent and HbA1c Level

Adherence to taking medication is essential for patients with chronic diseases such as Type 2 Diabetes Mellitus (T2DM). There have been many studies about the association between medication adherence and HbA1c levels, but few have used Adherence Refills and Medications Scale (ARMS) questionnaire and Proportion of Days Covered (PDC) method to measure adherence in Indonesian population. The aim of this study were to assess the association of medication adherence to HbA1c levels and compare two methods of adherence measurements. This research was conducted at Pasar Minggu Public Health Center, Jakarta using a cross-sectional design. The adherence assessment was conducted using a validated Indonesian version of the ARMS questionnaire and compared to the pharmacy refill adherence method using the PDC calculation. One hundred twenty-seven T2DM patients (75.6% female) with mean age of 58.69 years were recruited. The proportion of adhere patients as measured by ARMS was only 39.4% (50/127). Meanwhile, the proportion of adhere patients as measured by PDC was 77.2% (98/127). Adherence by both measurement showed significant associations with HbA1c <7% (ARMS, OR 4.000 (95% CI 1.705 – 9.386), p = 0.002; PDC, OR 5.674 (95% CI 1.266 – 25.438), p = 0.024). After controlled by covariates, the result remained significant (ARMS, aOR 4.281 (95% CI 1.785 – 10.267, p = 0.001; PDC, aOR 5.83 (95% CI 1.287 – 26.405), p = 0.022). Adherence and HbA1c levels was significantly associated even after controlling covariates. ARMS and PDC generated different proportions of adhere patients and may indicate the need of combining the two methods in measuring adherence.