Oral Antihyperglycemic Agents Research Articles

Formulation And Evaluation Of MucoadhesiveBuccal Tablets (Repaglinide) For Management Of Diabetes

Repaglinide is an oral antihyperglycemic agent used for the treatment ofnon-insulin-dependent diabetes mellitus. Themain objective of the studywas to formulate and evaluatebioadhesivebuccaltablets to avoid the first pass metabolismin liver. Bioadhesive buccal tablets were prepared by direct compression methodusingbioadhesive polymers likeHPMCK4 M,HPMC K15 M,Chitosan,HPMC K100 M,Sodium CMC,Carbopol 974 P,Sodium Alginate,Gum karayaandCarbopol 941NFin different ratios. The physicochemical compatibility of drug and polymers was studied by FT-IRspectroscopy.Prepared tablets were evaluated forpermeation study through porcine buccal mucosa, in vitrodrug release, bioadhesion strength, swelling index, moisture absorbance, surface pH.

Perspective of SGLT2 Inhibition in Treatment of Conditions Connected to Neuronal Loss: Focus on Alzheimer's Disease and Ischemia-Related Brain Injury.

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are oral anti-hyperglycemic agents approved for the treatment of type 2 diabetes mellitus. Some reports suggest their presence in the central nervous system and possible neuroprotective properties. SGLT2 inhibition by empagliflozin has shown to reduce amyloid burden in cortical regions of APP/PS1xd/db mice. The same effect was noticed regarding tau pathology and brain atrophy volume. Empagliflozin presented beneficial effect on cognitive function, which may be connected to an increase in cerebral brain-derived neurotrophic factor. Canagliflozin and dapagliflozin may possess acetylcholinesterase inhibiting activity, resembling in this matter Alzheimer’s disease-registered therapies. SGLT2 inhibitors may prove to impact risk factors of atherosclerosis and pathways participating both in acute and late stage of stroke. Their mechanism of action can be related to induction in hepatocyte nuclear factor-1α, vascular endothelial growth factor-A, and proinflammatory factors limitation. Empagliflozin may have a positive effect on preservation of neurovascular unit in diabetic mice, preventing its aberrant remodeling. Canagliflozin seems to present some cytostatic properties by limiting both human and mice endothelial cells proliferation. The paper presents potential mechanisms of SGLT-2 inhibitors in conditions connected with neuronal damage, with special emphasis on Alzheimer’s disease and cerebral ischemia.

A Nurse Practitioner-Led Multidisciplinary Diabetes Clinic for Adult Patients Discharged From Hospital

ObjectivesIn this study, we evaluated the feasibility of a nurse practitioner-led outpatient clinic (NPC) to facilitate the safe transition of patients with diabetes receiving insulin therapy between hospital and the community. MethodsAn NPC was set up to manage patients who had diabetes education in hospital and who were discharged on insulin. In addition to patient demographics and admission diagnosis, days seen postdischarge, duration of follow up, diabetes interventions and discharge care plan were recorded. For quality improvement, patients were asked to complete a questionnaire at the time of discharge from the NPC. ResultsWithin a 12-month period, 71 patients with diabetes attended the NPC 3 to 21 days after discharge and they were followed for 1 to 98 days. Thirteen patients required management of hypoglycemia and 56 patients had adjustment of medications to basal/prandial insulin or switched to oral antihyperglycemic agents. Fifty-four patients were returned to the care of their family physicians and 18 patients required a referral to a diabetes specialist. A postclinic questionnaire indicated that the clinic enabled patients to improve management of their diabetes. However, communication of the diabetes management plan to the family physician was an identified concern. ConclusionsAn NPC clinic can provide timely management and is a viable option to ensure safe transition of patients with diabetes from hospital back to their family physicians.

Monitoring and management of hyperglycemia in patients with advanced diabetic kidney disease.

Diabetes mellitus is the leading cause of end-stage renal disease, and uncontrolled hyperglycemia is directly related to the increased mortality in this setting. As kidney function decreases, it becomes more challenging to control blood glucose since the risk of hypoglycemia increases. Decreased appetite, changes in glycaemia homeostasis, along with reduced renal excretion of anti-hyperglycemic drugs tend to facilitate the occurrence of hypoglycemia, despite the paradoxical occurrence of insulin resistance in advanced kidney disease. Thus, in patients using insulin and/or oral anti-hyperglycemic agents, dynamic adjustments with drug dose reduction or drug switching are often necessary. Furthermore, in addition to consider these pharmacokinetics alterations, it is of utmost importance to choose drugs with proven cardio-renal benefits in this setting, such as sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide 1 receptor agonists. In this review, we summarize the indications and contraindications, titration of doses and side effects of the available anti-hyperglycemic agents in the presence of advanced diabetic kidney disease (DKD) and dialysis, highlighting the risks and benefits of the different agents. Additionally, basic renal function assessment and monitoring of glycemic control in DKD will be evaluated in order to guide the use of drugs and define the glycemic targets to be achieved.

Continuing Challenges in The Medical Management of Gestational Diabetes Mellitus

The management of gestational diabetes mellitus (GDM) involves screening (or universal testing), a diagnostic oral glucose tolerance test, patient counselling/education, gestational weight management and medical nutrition therapy, and self-monitoring of blood glucose levels with regular glycaemia reviews. This is in addition to pharmacological treatment, often insulin therapy, if glycaemia is above target. Females with GDM receive more frequent ultrasound testing to assess fetal growth, and birth is planned and not usually allowed to go much past term. A range of challenges continue to arise in GDM management including screening approaches and diagnostic criteria, dealing with the increasing numbers of females diagnosed, weight and glycaemic targets, the long-term safety of oral antihyperglycaemic agents for the offspring, particularly metformin, and adjunct medication for complication prevention. GDM management involves additional complexities including differentiating between those with likely undiagnosed Type 2 diabetes mellitus (diabetes in pregnancy), how to manage females with high glucose early in pregnancy less than diabetes in pregnancy, and identifying females with rare causes, for example monogenic diabetes or new Type 1 diabetes mellitus in pregnancy. While the management of GDM has evolved from identifying females at high risk of progressing to Type 2 diabetes mellitus, to greater focus on improving pregnancy outcomes, females with prior GDM and their offspring have the highest need for follow-up and prevention strategies. To date, follow-up and intervention remains limited for this high-risk group for both diabetes and cardiovascular disease. Follow-up in these females is particularly important for the next pregnancy, especially as GDM prevention from the second trimester onwards remains another continuing challenge.

Tip 2 DM hastalarında antihiperglisemik ilaç kullanımı ile MPV ve PDW düzeylerinin değerlendirilmesi

Objectives: MPV and PDW are vascular complications markers and improved glycemic control levels are correlated those indicators in patients with type 2 Diabetes Mellitus. The aim of in this study, MPV and PDW levels were compared type 2 diabetic patients treated with oral antihyperglycemic agent and insulin. Methods: This study was performed retrospectively on type 2 DM patients who were admitted to Ankara Atatürk Training and Research Hospital. 118 randomly selected patients were divided into 3 groups that were non-diabetic (Group 1), who received OAD therapy (Group 2), and those who received insulin therapy (Group 3). HbA1c, MPV, PDW levels were collected, analyzed and compared with each other. Results: MPV and PDW values were increased in type 2 DM patients compared to the control group (Group 2; p <0.001 and Group 3 p <0.001, respectively). There was no statistically significant difference between MPV and PDW values in patients treated OAD and insulin therapy (p=0.736 ve p=0.360 respectively). A statistically significant positive correlation was found between HbA1c values and MPV (p <0.001) and PDW (p <0.001) values. Conclusions: In our study, no significant difference was found between MPV and PDW values of patients using insulin and oad. Early initiation of conventional insulin therapy in patients with type 2 diabetes provides good glycemic control. Rational drug use in accordance with the guidelines; gains importance in treatment success. Skipping this factor may reduce the efficiency of other efforts in relation to rational treatment.

Destek tedavisi D vitamininin yıllık ritmini bozar: Retrospektif bir analiz

Objectives: MPV and PDW are vascular complications markers and improved glycemic control levels are correlated those indicators in patients with type 2 Diabetes Mellitus. The aim of in this study, MPV and PDW levels were compared type 2 diabetic patients treated with oral antihyperglycemic agent and insulin. Methods: This study was performed retrospectively on type 2 DM patients who were admitted to Ankara Atatürk Training and Research Hospital. 118 randomly selected patients were divided into 3 groups that were non-diabetic (Group 1), who received OAD therapy (Group 2), and those who received insulin therapy (Group 3). HbA1c, MPV, PDW levels were collected, analyzed and compared with each other. Results: MPV and PDW values were increased in type 2 DM patients compared to the control group (Group 2; p <0.001 and Group 3 p <0.001, respectively). There was no statistically significant difference between MPV and PDW values in patients treated OAD and insulin therapy (p=0.736 ve p=0.360 respectively). A statistically significant positive correlation was found between HbA1c values and MPV (p <0.001) and PDW (p <0.001) values. Conclusions: In our study, no significant difference was found bet-ween MPV and PDW values of patients using insulin and oad. Early initiation of conventional insulin therapy in patients with type 2 diabetes provides good glycemic control. Rational drug use in accordance with the guidelines; gains importance in treatment success. Skipping this factor may reduce the efficiency of other efforts in relation to rational treatment.

Management of type 2 diabetes for prevention of cardiovascular disease. An expert opinion of the Italian Diabetes Society

AimsType 2 diabetes mellitus is characterized by an increased risk of developing long-term cardiovascular complications. Several underlying mechanisms have been proposed for the diabetes-related increase in cardiovascular risk, i.e. chronic hyperglycemia, duration of the disease, drug-induced hypoglycemia, coexistence of multiple cardiovascular risk factors, etc. In the last few years, new pharmacological approaches capable of treating chronic hyperglycemia without increasing the risk of hypoglycemia have emerged for the treatment of diabetes. Data synthesisWith data mainly obtained from randomized controlled trials recruiting patients with type 2 diabetes in secondary prevention of cardiovascular disease, some of these newer antihyperglycemic drugs have shown to significantly reduce the risk of cardiovascular disease. In addition, the combined control of traditional cardiovascular risk factors, e.g. dyslipidemia, hypertension, etc., has demonstrated to be effective in reducing the burden of cardiovascular diseases in patients with type 2 diabetes. ConclusionsIn this document written by some experts of the Italian diabetes society (SID), we will focus our attention on oral antihyperglycemic agents for people with type 2 diabetes in primary or secondary prevention of cardiovascular disease, excluding for brevity the injection therapies for diabetes, such as insulin and glucagon-like peptide-1 receptor agonists.

1076-P: A 12-Week Treatment with Ciclosporin A Improves Insulin Secretion in Patients with Adult-Onset Autoimmune Diabetes: An Open-Label, Single-Arm, Pilot Study

Objectives: Adult-onset autoimmune diabetes, defined as having latent autoimmune diabetes in adults (LADA), is characterized by a less intensive autoimmune process, in which a lymphocytic infiltration of the exocrine pancreas is involved. immunosuppressive agents may have potential therapeutic benefit. This is a pilot study examining the therapeutic effects of ciclosporin A on insulin secretion in patients with LADA. Methods: The study was an open label, single arm, pilot trial. A total of 18 patients (12 men and 6 women with mean age of 40.6 yrs old) diagnosed with LADA were prospectively evaluated. All patients underwent insulin treatment at least for 3 months without any oral anti-hyperglycemic agent. All patients were prescribed ciclosporin A (50mg/day) for 12 weeks. Serum C-peptide concentrations were measured at baseline and 3 months after ciclosporin A intervention. We also evaluated total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine (Cre) before and after ciclosporin A treatment. The primary outcome of the study was the change in serum C-peptide concentrations. Results: A total of 17 patients completed the study. One patient was withdrawn at day 32 due to discontinuation of medication. Serum fasting C-peptide concentrations significantly increased from 0.12 ng/ml up to 0.32 ng/ml (P<0.001). After 12-week ciclosporin A intervention, there was no significant difference on TBIL (14.65 vs. 12.83umol/L, P>0.05), DBIL (4.70 vs. 4.65 umol/L, P>0.05), AST (17.41 vs. 17.82 U/L, p>0.05), ALT (18.19 vs. 18.08 U/L, p>0.05), or Cre (67.40 vs. 67.53 umol/L, P>0.05) compared with the corresponding baseline levels. Conclusions: This pilot study demonstrates the potential therapeutic effects of oral administration of ciclosporin A for patients with LADA. Larger, controlled studies are needed to verify the findings. Disclosure L. Zhang: None. W. Meng: None. S. Chen: None. Y. Yang: None. J. Wang: None. Y. Dong: None.

1026-P: Physician-Related Factors Associated with Delay Insulin Initiation in Type 2 Diabetes Mellitus Patients with Oral Antihyperglycemic Agent Treatment Failure

Aims: Despite the availability of numerous glucose-lowering therapies and clear guidelines for T2DM management, only 1/3 of the patient with T2DM in Thailand can achieve their glycemic targets. Timely initiation of insulin therapy has been suggested as one of the strategies to solve this problem. Therefore, the purpose of this study was to identify physician’s attitudes among the internal medicine residents regarding insulin initiation. Methods: The questionnaire adapting from Physician Attitudes to Insulin Therapy questionnaire was used to conduct a questionnaire-based survey among the internal medicine residents in Siriraj Hospital, Mahidol University. Results: The questionnaire was sent to 100 internal medicine residents. The response rate was 80%. The majority of respondents (60%, n=48/80) were willing to initiate insulin therapy for the patients with T2DM, who failed oral antihyperglycemic drug (OHD) treatment at HbA1c level between 7.5-9.5%. In addition, 45% (n=36/80) of respondents use HbA1c threshold of above 8.5% to initiate insulin treatment add on to OHD. However, if the internal medicine residents themselves were diabetes mellitus, they would decide to receive insulin at HbA1c level between 7.0-8.5%. The main reasons regarding insulin initiation barrier by physicians were a consideration of burden on the patients and families to initiate insulin therapy (88%, n=70/80), time-consuming for an explanation about insulin devices, monitoring and adjustment (74%, n=59/80) and difficult to advise the patients who fear the injection drugs to use insulin (70%, n=56/80). Conclusions: Physician-related factors associated with delay insulin initiation need to be addressed for better diabetes management. Internal medicine resident aspects according to high HbA1c thresholds, high effort regarding explanation, and motivation, and the patients and family burdens are the main barriers for insulin initiation. Disclosure T. Sitasuwan: None. S. Choksakunwong: None. W. Srivanichakorn: None.

Effects of Obesity and Short-Term Metformin Treatment on Liver Steatosis in Female Zucker Rats

Abstract Objectives Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disease in adolescents in the US and World, and the risk has increased with the rise in obesity. We reported that obesity increases Fatty liver (steatosis) using an obese Zucker rat model. Metformin is an oral anti-hyperglycemic agent approved by the FDA to treat type 2 diabetes (T2D) in adults and children older than 10 years of age. There is insufficient evidence regarding the effects of metformin in pediatric liver steatosis. The objective of this study was to investigate the effects of short-term metformin treatment on liver steatosis and related serum markers for liver damage. Methods Five week old lean (n = 16) and obese (n = 16) female Zucker rats after one week of acclimation, received AIN-93 G diet for 8 weeks to induce NAFLD. After 8 weeks, lean and obese rats were randomly assigned to the following four groups (8 rats/group): 1) lean without metformin (LC), 2) lean with metformin (LMet), 3) obese without metformin (ObC), and 4) obese with metformin (ObMet). Metformin were mixed with AIN-93 G diet at 1000 mg/kg of diet. Rats were weighed twice per week. All rats were sacrificed 10 weeks post-metformin treatment and serum and livers were collected. Steatosis was semiquantitated as a score of 1 to 4 based upon the relative degree of steatosis within hepatocytes: 1) < 25%, 2) 25–50%, 3) 50–75%, and 4) >75%. Serums were collected to measure the levels of Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) on a clinical analyzer. Results Obese rats gained significantly more weight (P < .001) than lean rats for both control and Metformin treatment groups and there was no significant difference between ObC vs. ObMet group (P = 0.20). The mean + SD liver steatosis scores for the LC, LMet, ObC and ObMet groups were 0.13 + o.3, 0.13 + o.3, 3.67 + 0.52 and 3.00 + 0.82. The ObMet treated rats had lower (P < 0.04) liver steatosis than ObC rats. There were no significant differences for the serum ALT and AST levels between groups. However, obesity increased significantly (P < 0.01) serum AST levels compared to LC but not in the metformin group. Conclusions In summary, in the obese zucker rat model, short-term metformin treatment decreased liver steatosis but did not impact serum markers of liver steatosis. Funding Sources Arkansas Children Research Institute/Arkansas Bioscience Institute.

Glycemic Monitoring and Management in Advanced Chronic Kidney Disease.

Glucose and insulin metabolism in patients with diabetes are profoundly altered by advanced chronic kidney disease (CKD). Risk of hypoglycemia is increased by failure of kidney gluconeogenesis, impaired insulin clearance by the kidney, defective insulin degradation due to uremia, increased erythrocyte glucose uptake during hemodialysis, impaired counterregulatory hormone responses (cortisol, growth hormone), nutritional deprivation, and variability of exposure to oral antihyperglycemic agents and exogenous insulin. Patients with end-stage kidney disease frequently experience wide glycemic excursions, with common occurrences of both hypoglycemia and hyperglycemia. Assessment of glycemia by glycated hemoglobin (HbA1c) is hampered by a variety of CKD-associated conditions that can bias the measure either to the low or high range. Alternative glycemic biomarkers, such as glycated albumin or fructosamine, are not fully validated. Therefore, HbA1c remains the preferred glycemic biomarker despite its limitations. Based on observational data for associations with mortality and risks of hypoglycemia with intensive glycemic control regimens in advanced CKD, an HbA1c range of 7% to 8% appears to be the most favorable. Emerging data on the use of continuous glucose monitoring in this population suggest promise for more precise monitoring and treatment adjustments to permit fine-tuning of glycemic management in patients with diabetes and advanced CKD.

Acute Renal Failure, Ketoacidosis, and Urogenital Tract Infections with SGLT2 Inhibitors: Signal Detection Using a Japanese Spontaneous Reporting Database.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a class of oral anti-hyperglycemic agents that have been available on the market in Japan since 2014. Although safety information has accumulated alongside the clinical use, the warnings issued by each country based on adverse events associated with the drug are different and examination of the safety of the drug is insufficient. This study examined the safety of SGLT2 inhibitors by using a Japanese spontaneous reporting database and focusing on the cautions issued in each country and the disparities within existing research into the occurrence of the adverse events of acute renal failure (ARF), ketoacidosis, and urogenital tract infections (UTIs). We analyzed data recorded on the Japanese Adverse Drug Event Report database (JADER) between April 2014 and February 2019. We calculated the reporting odds ratio (ROR) and 95% confidence interval (CI) with sex and age as adjustment factors. JADER contained 366,501 cases with the adverse events of interest; 4322 involved SGLT2 inhibitors. The ROR for SGLT2 inhibitors was calculated as 1.0 (95% CI 0.9-1.2) for ARF, 72.2 (95% CI 59.3-87.8) for ketoacidosis, and 14.0 (95% CI 11.0-17.8) for UTIs. Analysis of only subjects receiving treatment for diabetes showed a similar trend. The results suggested a correlation between SGLT2 inhibitors and the onset of ketoacidosis and UTIs, but not between SGLT2 inhibitors and ARF. Further verification of the safety of SGLT2 inhibitors, through continued risk assessments and large-scale clinical studies, are necessary.

Bioactive Components and Health Benefits of Saskatoon Berry.

In response to the recent rise in numbers of diabetes patients, many treatments have been developed; but currently, oral antihyperglycemic agents and insulin are still the main clinical treatments. Since current drugs have limitations and harmful side effects, research in alternative treatments has been sought. This article reviews recent research updates of Saskatoon berries (SB), covering its background information, its main active ingredients, its structure, and its function. Flavonoid compounds in Saskatoon berries, in particular flavanol, anthocyanin, and proanthocyanin, possess anti-inflammatory, antitumor, and antidiabetes impacts. The current review synthesizes the latest research on the health benefits of Saskatoon berry in a variety of domains. With further research, SB has the potential to help treat and prevent diabetes in the future.

MON-475 Discrepant Thyroid Function Tests in Adenocarcinoma-Is This a True Thyroid Disorder?

Background: Many causes of abnormal thyroid function tests (TFTs) occur that may or may not reflect a true thyroid disorder. The most common include: immune check point inhibitors therapies (ICI) used to treat various types of cancers; biotin supplements, which may interfere with thyroid function test assays; euthyroid sick syndrome; as well as amiodarone therapy for cardiac disorders. Clinical Case: A 67-year old female patient with type 2 diabetes mellitus, taking insulin and oral antihyperglycemic agents, with hyperlipidemia, hypertension and coronary artery disease, who had abnormal TFTs (TSH was 3.7 to 4.9 uIIu/ml; ref range 0.27-4.2 uIU/mL), and Free T4 was 0.92 to 1.06 ng/dL; ref range 0.55-1.6 ng/dl) prior to the diagnosis of metastatic adenocarcinoma of the lungs. She was initially treated with radiation. TFTs were unchanged. Her CEA was noted to be 129.5 (0-3.0 ng/mL). However, following chemotherapy with Tarceva (Erlotinib) 50 mg po daily, the TSH increased to 7.6 uIU/ml with Free T4 of 3.19 ng/dL. She remained clinically euthyroid. A thyroid ultrasound showed 1 -small sub centimeter nodule in each thyroid lobe. The patient later admitted to also taking biotin for an unknown period of time. TSH antibodies and TSI were both negative. Free T4 by dialysis was normal. While still taking Tarceva her TSH was noted to be 2.5 to 3.8 uIU/ml and both Free T4 and Free T3 were elevated and was 6.57 pg/ml;ref range=2.52-4.34 pg/mL). Six months later, the Free T4 decreased to 1.08 ng/dL. Thyroid antibodies and thyroglobulin remain normal. The patient remained clinically euthyroid. Conclusion: It is important to note that several factors can cause abnormal thyroid function tests, such as Immune check point inhibitors therapy, with the exact mechanism for abnormal TFTs unknown, and can also be associated with either Grave’s hyperthyroidism or Hashimoto’s hypothyroidism,as well as other autoimmune endocrine disorders. Biotin, a common supplement, has also been reported to interfere with the thyroid function test assays for free thyroxine (T4), total T4, free triiodothyronine (T3), total T3, TSH, and various cancer markers. However, It is important to clinically evaluate the patient for thyroid disorders, and recognize that therapy may not always be required, when discrepant and fluctuating thyroid function tests are obtained, such as in this patient.

MON-690 Euglycemic Diabetic Ketoacidosis Associated with SGLT-2 Inhibitors- an Under-recognized Diagnosis

BackgroundSodium glucose cotransporter-2 inhibitors (SGLT-2i) are a promising class of oral anti-hyperglycemic agents with mounting evidence of reduced cardiovascular risk and renal failure, in patients with type 2 diabetes mellitus. Recent increase in their use has led to identification of hitherto unknown side effects of these drugs. Euglycemic Diabetic Ketoacidosis (eDKA), found to be associated with SGLT-2i use, is a life-threatening condition and commonly goes unrecognized due to absence of the cardinal sign of hyperglycemia.Clinical CaseWe describe a 47 year old male with history of coronary artery disease and recently diagnosed type 2 diabetes mellitus who presented to our hospital with one week history of nausea, lethargy, progressive fatigue, and shortness of breath. He was diagnosed with type 2 diabetes three weeks prior, with HBA1c of 12%.His regimen included basal insulin and recent transition to empagliflozin due to severe GI intolerance with metformin use.On arrival he was noted to be tachycardic with a heart rate of 113/min, afebrile and normotensive. Physical exam was mostly unremarkable except for dry oral mucous membranes. Serum chemistry was consistent with high anion gap metabolic acidosis with bicarbonate of 6.9 mmol/L (21-32 mmol/L), anion gap of 29 mmol/L (10-20 mmol/L), mildly elevated blood glucose of 132 mg/dl (74-106 mg/dl), acute kidney injury with creatinine of 1.47 mg/dl (0.7- 1.3 mg/dl), and a beta hydroxybutyrate level of 82.7 mg/dl (0.20- 5.63 mg/dl). Urine analysis showed ketonuria. This was consistent with a clinical and biochemical diagnosis of eDKA. He was treated with IV D5%NS-20mEq/L KCL and an insulin drip. Upon resolution of his acidosis and normalization of the anion gap he was switched to subcutaneous Insulin Glargine and Lispro. Empagliflozin was held as it was thought to be contributing to the diagnosis of eDKA.ConclusionOur case yet again illustrates the importance of recognition of EDKA to aid prompt management, especially with the rising popularity of SGLT-2 inhibitors. It is also important to educate patients about this condition, mostly notable in the first two months of starting the medication, to recognize the concerning symptoms and precipitating factors like dehydration, improper insulin dosing, low calorie diet, alcohol, infection, surgery. An acceptable alternative to SGLT-2i can be glucagon like peptide receptor (GLP- 1) agonists, also associated with good cardiovascular outcomes.

Sodium-glucose cotransporter-2 inhibitors: updated evidence on their efficacy and safety in patients with type-2 diabetes

Management of type-2 diabetes mellitus (T2DM) is challenging. The scope of existing therapies toward T2DM has transformed remarkably. These large assortments of therapies have produced evidence-based data. Sodium-glucose cotransporter-2 inhibitor (SGLT-2i) is the most recent class of oral anti-hyperglycemic agents. They are approved by Food and Drug Administration for the treatment of diabetes mellitus. SGLT-2i has a unique mechanism of action and that lower glucose independent of insulin. They reduce renal tubular glucose reabsorption, thereby lowering blood glucose without stimulating the release of insulin. Additional advantages involve suitable effects on blood pressure and weight. According to guidelines of the American Association of Clinical Endocrinologists/ the American College of Endocrinology 2016, SGLT-2i (in the form of canagliflozin, dapagliflozin, and empagliflozin) is one of the acceptable alternatives to metformin as initial therapy towards T2DM. Canagliflozin, dapagliflozin, and empagliflozin reduce the cardiovascular risk in comparison to placebo as the part of standard care. This review article focuses on the clinical trials published over the past year and specifically the metabolic aspect of SGLT-2i and the adverse effects related to SGLT-2 inhibitors.

Hypoglycemia in patients with type 2 diabetes treated with oral antihyperglycemic agents detected by continuous glucose monitoring: a multi-center prospective observational study in Croatia

BackgroundHypoglycemia in type 2 diabetes mellitus (T2DM) is still unsolved issue. The aim of this study was to investigate hypoglycemia in T2DM in participants treated with oral antihyperglycemic agents using different glucose cut-off values and to explore influence of different therapies.MethodsThis multi-center prospective observational study included participant with T2DM from primary care offices across Croatia treated with antihyperglycemic agents who were monitored using professional continuous glucose monitoring (CGM) device (iPro™2). Hypoglycemia was defined as at least 1% of the monitored period spent in the hypoglycemic range and/or area under the curve of glycemia registered ever under the defined cut-off value. The higher upper limit of blood glucose cut-off value was 3.9 mmol/L (70 mg/dL) and the lower one 3.0 mmol/L (54 mg/dL).ResultsStudy included 94 participants. Median hemoglobin A1C levels, age, T2DM duration, body mass index, and CGM use duration were 7 (5.8–11.5) %, 65 (40–86) years, 7 (1–36) years, 30.4 (21.3–41.5) kg/m2 and 6 (1–7) days, respectively. Fifty participants were treated with sulfonylurea, primarily gliclazide (84%). The percentage of participant with hypoglycemia based on the higher cut-off value was 42.6% vs. 16% based on the higher cut-off value. The percentage of participant with nocturnal hypoglycemia (23 PM to 06 AM) was significantly lower among participant with hypoglycemia based on the higher cut-off value compared to lower one (7.8% vs. 22.9%). Sulfonylurea treatment did not influence the occurrence of hypoglycemia. Analysis of the data from participants having hypoglycemia based on the lower cut-off value pointed to other possible risk factors for hypoglycemia like prolonged overnight fasting, physical activity, alcohol consumption, and concomitant therapy with angiotensin-converting enzyme inhibitors.ConclusionsIn participant with T2DM treated with oral antihyperglycemic agents hypoglycemia based on the blood glucose cut-off value of 3.9 mmol/L was more prevalent, but with less nocturnal hypoglycemia. Sulfonylurea therapy was not risk factor for hypoglycemia regardless of cut-off value. In participants having hypoglycemia based on the blood glucose cut-off value of 3.0 mmol/L some other possible factors were identified related to concomitant therapy, nutrition and daily habits.Trial registrationClinicalTrials.gov Identifier: NCT03253237.

SAT-161 TREATMENT OF DIABESITY WITH DIET AND NEWER ANTIGLYCEMIC MEDICATIONS IN PLACE OF INSULIN: EFFECT ON DIABETIC KIDNEY DISEASE

Type 2 diabetes is the result of several years of prediabetes and the metabolic syndrome. The goal of treatment is weight loss to reduce insulin resistance, and to reduce the need for glucose-lowering medications including insulin. Long term data from the Diabetes Control and Complications trial showed that tight HbA1C correction does not lead to better cardiovascular disease (CVD) outcomes, yet tight control does correct microvascular complications. Recent reports suggested that insulin therapy does not treat the biochemical components of metabolic syndrome, whereas the oral antihyperglycemic medications especially metformin, the incretin mimetics (GLP-1 receptor agonists) and the sodium-glucose co-transporter-2 (SGLT2) inhibitors do indeed correct this. Weight loss correction also needs a caloric deficit but this becomes hard with insulin therapy which often causes weight gain. Standards of Medical Care in Diabetes by American Diabetes Association stated that SGLT2 inhibitors and GLP-1 RA should be considered for patients with type 2 diabetes, established atherosclerotic CVD and chronic kidney disease (CKD) who require another drug or cannot tolerate metformin to attain target HbA1C as these agents appear to reduce risks of CKD progression, CVD events, and hypoglycemia. We treated patients of type 2 diabetes and obesity with combined low-carbohydrate diets and intermittent fasting, along with metformin and newer antiglycemic agents, stopping of insulin therapy wherever feasible. The associations between weight loss, improvement in renal function and treatments were reported using correlation coefficient r and probability p value where significant. Total of 60 patients were reviewed between February 2014 and July 2019 in our outpatient clinic. Mean age was 62.5 years with male to female ratio 3:2. The observed average weight loss was 10.74kg, with 13.2kg and 7.06kg loss for male and female patients respectively. Estimated glomerular filtration rate (eGFR) has improved by 3.13ml/min/1.73m2 and proteinuria was reduced by 12.4 units on average, in terms of albumin creatinine ratio. Mean HbA1C reduction was 0.7%. Mean reduction in insulin therapy was by 16 units with a maximum 202 units in one patient. Clinic blood pressure measurement during the follow-up period was largely unchanged. Weight reduction seems to improve eGFR (r 0.2, p 0.0012, 95% CI from 3.6716 to 13.4304). Combined use of SGLT-2 inhibitor and GLP-1 RA seems to have effect on improvement in eGFR (p 0.01) regardless of weight loss.View Large Image Figure ViewerDownload Hi-res image Download (PPT) It seems possible to control blood sugar in type 2 diabetes by combining metformin, SGLT-2 inhibitor and or GLP-1 RA with intermittent fasting and low-calorie diets avoiding extra-insulin therapy, with resultant improvement in renal function (eGFR and proteinuria) along with weight loss. Therefore, oral antihyperglycemic agents with proven cardiovascular benefit and renal protection should be considered earlier to achieve the treatment goals where drug-specific effects are important on the basis of patient factors.

Sodium glucose cotransporter2 inhibitor-possible treatment for patients with diabetes, pulmonary disease and CO2 retention

Chronic pulmonary diseases such as chronic obstructive pulmonary disease, obstructive sleep apnea and obesity hypoventilation syndrome are common conditions which share decreased pulmonary ventilation and CO2 retention.CO2 is an end-product of metabolism of all body cells. When CO2 accumulates, it is recommended to consider measures to reduce its endogenous production. One such measure relates to the sources of energy ingested as nutrition. It is recommended to increase the intake of dietary lipids and reduce carbohydrates, as the former produces less endogenous CO2 when metabolized.Our hypothesis focuses on a different mechanism for reducing the availability of carbohydrates, especially glucose, as a fuel for body cells metabolism. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a new class of oral anti-hyperglycemic agents. Physiologically, glucose filtered through kidney glomeruli is reabsorbed in the proximal convoluted tubule; SGLT2i inhibit this mechanism. Therefore, glucose is secreted in the urine (glucosuria) and as a result glucose serum level is reduced. If glucose serum level is reduced, less glucose is available for metabolism, less CO2 is endogenously produced, and less CO2 must be expelled from the diseased lungs.It is hypothesized that these agents may be beneficial for patients with diabetes and concomitant pulmonary disease who retain CO2.