Prandimet (repaglinide/metformin) / Shionogi, Novo Nordisk - LARVOL DELTA

An Overlooked Cause of Hypoglycemia and Weight Loss: Phosphodiesterase-4 Inhibitors (ENDO 2024) - "Background: Phosphodiesterase-4 (PDE-4) inhibitors, apremilast and roflumilast, are anti-inflammatory agents used to treat psoriasis, psoriatic arthritis, and COPD...Prior to this, her A1c was 7.8% and weight 104 kg on stable doses of metformin, repaglinide, and insulin glargine... Significant weight loss with apremilast may be explained by PDE-4 inhibition increasing cyclic AMP, which triggers the release of GLP-1 with subsequent effects on pancreatic beta cells. Apremilast has also been shown to significantly increase fasting insulin levels in patients without insulin resistance, as seen in our patient (1). Given these effects, patients may be at higher risk of hypoglycemia with concurrent glucose-lowering agents, particularly secretagogues."

Chronic Obstructive Pulmonary Disease • Dermatology • Endocrine Cancer • Endocrine Disorders • Gastrointestinal Disorder • Genetic Disorders • Hypoglycemia • Immunology • Inflammatory Arthritis • Obesity • Oncology • Psoriasis • Psoriatic Arthritis • Pulmonary Disease • Respiratory Diseases • Rheumatology • Seronegative Spondyloarthropathies • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma • Type 2 Diabetes Mellitus • IGF1 • IGF2

UNLOCKING TAILORED THERAPIES FOR MODY1 DIABETES USING GLUCOSE SENSORS: A SINGLE‐PATIENT CASE REPORT (ATTD 2024) - "After the genetic response, we replaced Metformin with Repaglinide based on glucose patterns. Initially, lifestyle modifications yielded a Time in Range (TIR) of 75% and Glucose Management Indicator (GMI) of 7%. While long-acting sulfonylureas remain the preferred therapy for MODY1, this case underscores the potential utility of sensor-derived glucose patterns as valuable tools in guiding tailored treatments. Such an approach offers the promise of preventing both hypoglycaemic events and the onset of microvascular complications, heralding a new era of precision medicine in the management of MODY1 diabetes."

Clinical • Diabetes • Hypoglycemia • Metabolic Disorders • Renal Disease • Type 2 Diabetes Mellitus

Missed MODY With Complex Mutation (ENDO 2023) - "He was diagnosed with type 2 diabetes mellitus at the age of 13 years and was initially treated with insulin which was subsequently transitioned to repaglinide and metformin. MODY is a rare condition and because of its wide clinical presentation, it is common for it to be missed. There are about 14 subtypes of MODY with different genetic mutations, each affecting the beta cell function in a different way. Our case is unique given that our patient had two genetic mutations."

Late-breaking abstract • Diabetes • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus • HNF1A

In Vivo Evaluation of Nanoemulsion Formulations for Metformin and Repaglinide Alone and Combination. (PubMed, J Pharm Sci) - "A statistically significant decrease was observed in the blood glucose values of the diabetic rats treated with nanoemulsion formulations containing active substance/substances, compared to diabetic rats (control) (p<0.05). Nanoemulsion formulations (especially nanoemulsion containing metformin HCl and repaglinide combination) have a better antidiabetic activity and are more effective in reducing oxidative stress caused by diabetes."

Journal • Preclinical • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

IgG4-Related Autoimmune Pancreatitis Following RNA-Based COVID-19 Vaccination (ACG 2022) - "He was started on metformin and repaglinide but his blood sugar remained uncontrolled...He was started on prednisone 40mg daily with a tapering schedule...(B, C) Hypervascular arterial enhancing pancreatic head mass measuring up to 3.6 x 2.6 x 5.5 cm in the largest dimensions (D) Compared to prior studies (previous images), the pancreas is no longer swollen and edematous but appears somewhat atrophic. No definite enhancing masses seen in the head of the pancreas."

Anemia • Cholestasis • Dermatology • Diabetes • Fatigue • Gastroenterology • Hematological Disorders • Hepatitis B • Hepatology • Immunology • Infectious Disease • Inflammation • Metabolic Disorders • Novel Coronavirus Disease • Oncology • Pancreatitis • Pruritus

Unexpected side effect in the elderly (EUSEM 2022) - "Usual treatment: Metformin, Repaglinide, omeprazole, Rivaroxaban, candesartan, furosemide, bisoprolol, digoxin.Assessed two days before in our Emergency Department due to the sudden appearance of a very pruritic anterior chest rash, associated with predominantly perioral and periocular facial edema, and bullous lesions, some with hemorrhagic content, in the oral cavity, with a sensation of mild dysphagia to solids and liquids; no recent changes in food or hygiene and/or cleaning products. Currently in treatment with paracetamol due to catarrhal symptoms...It is usually triggered by drugs, including mirtazapine. A highly suspect is mandatory due to its letality."

Adverse events • Clinical • Acute Kidney Injury • Atrial Fibrillation • Cardiovascular • Congestive Heart Failure • Critical care • Depression • Dermatology • Diabetes • Diabetic Nephropathy • Gastrointestinal Disorder • Heart Failure • Hematological Disorders • Hepatology • Liver Failure • Metabolic Disorders • Nephrology • Novel Coronavirus Disease • Pain • Pulmonary Disease • Renal Disease • Steven-Johnson Syndrome • Type 2 Diabetes Mellitus

Unexpected side effect in the elderly (EUSEM 2022) - "Usual treatment: Metformin, Repaglinide, omeprazole, Rivaroxaban, candesartan, furosemide, bisoprolol, digoxin.Assessed two days before in our Emergency Department due to the sudden appearance of a very pruritic anterior chest rash, associated with predominantly perioral and periocular facial edema, and bullous lesions, some with hemorrhagic content, in the oral cavity, with a sensation of mild dysphagia to solids and liquids; no recent changes in food or hygiene and/or cleaning products. Currently in treatment with paracetamol due to catarrhal symptoms...It is usually triggered by drugs, including mirtazapine. A highly suspect is mandatory due to its letality."

Adverse events • Clinical • Acute Kidney Injury • Atrial Fibrillation • Cardiovascular • Congestive Heart Failure • Critical care • Depression • Dermatology • Diabetes • Diabetic Nephropathy • Gastrointestinal Disorder • Heart Failure • Hematological Disorders • Hepatology • Liver Failure • Metabolic Disorders • Nephrology • Novel Coronavirus Disease • Pain • Pulmonary Disease • Renal Disease • Steven-Johnson Syndrome • Type 2 Diabetes Mellitus

Unexpected side effect in the elderly (EUSEM 2022) - "Usual treatment: Metformin, Repaglinide, omeprazole, Rivaroxaban, candesartan, furosemide, bisoprolol, digoxin.Assessed two days before in our Emergency Department due to the sudden appearance of a very pruritic anterior chest rash, associated with predominantly perioral and periocular facial edema, and bullous lesions, some with hemorrhagic content, in the oral cavity, with a sensation of mild dysphagia to solids and liquids; no recent changes in food or hygiene and/or cleaning products. Currently in treatment with paracetamol due to catarrhal symptoms...It is usually triggered by drugs, including mirtazapine. A highly suspect is mandatory due to its letality."

Adverse events • Clinical • Acute Kidney Injury • Atrial Fibrillation • Cardiovascular • Congestive Heart Failure • Critical care • Depression • Dermatology • Diabetes • Diabetic Nephropathy • Gastrointestinal Disorder • Heart Failure • Hematological Disorders • Hepatology • Liver Failure • Metabolic Disorders • Nephrology • Novel Coronavirus Disease • Pain • Pulmonary Disease • Renal Disease • Steven-Johnson Syndrome • Type 2 Diabetes Mellitus

Unexpected side effect in the elderly (EUSEM 2022) - "Usual treatment: Metformin, Repaglinide, omeprazole, Rivaroxaban, candesartan, furosemide, bisoprolol, digoxin.Assessed two days before in our Emergency Department due to the sudden appearance of a very pruritic anterior chest rash, associated with predominantly perioral and periocular facial edema, and bullous lesions, some with hemorrhagic content, in the oral cavity, with a sensation of mild dysphagia to solids and liquids; no recent changes in food or hygiene and/or cleaning products. Currently in treatment with paracetamol due to catarrhal symptoms...It is usually triggered by drugs, including mirtazapine. A highly suspect is mandatory due to its letality."

Adverse events • Clinical • Acute Kidney Injury • Atrial Fibrillation • Cardiovascular • Congestive Heart Failure • Critical care • Depression • Dermatology • Diabetes • Diabetic Nephropathy • Gastrointestinal Disorder • Heart Failure • Hematological Disorders • Hepatology • Liver Failure • Metabolic Disorders • Nephrology • Novel Coronavirus Disease • Pain • Pulmonary Disease • Renal Disease • Steven-Johnson Syndrome • Type 2 Diabetes Mellitus

Principal Component Analysis and DoE-Based AQbD Approach to Multipurpose HPTLC Method for Synchronous Estimation of Multiple FDCs of Metformin HCl, Repaglinide, Glibenclamide and Pioglitazone HCl. (PubMed, J Chromatogr Sci) - "The developed method can synchronously analyze multiple FDCs of MET which required several chromatographic methods. Hence, the present method is multipurpose-HPTLC for the synchronous estimation of multiple FDCs of MET which required minimum organic solvent, time and cost of analysis."

Journal • Diabetes • Metabolic Disorders

Comparison of Metformin and Repaglinide Monotherapy in the Treatment of New-Onset Type 2 Diabetes Mellitus. (PubMed, Cureus) - "Conclusion Our study concluded that both metformin and repaglinide have similar anti-hyperglycemic effects. Repaglinide can be prescribed as an alternative drug to metformin in patients with new-onset diabetes mellitus."

Journal • Monotherapy • Diabetes • Dyslipidemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Novo Nordisk Intends to Appeal Adverse Ruling in Prandin® (repaglinide) Patent Case (PRNewswire) -

US District Court issued an adverse ruling in a patent litigation case regarding Novo Nordisk's US Patent No. 6,677,358 that the patent, which covers the combination use of repaglinide and metformin for the treatment of type 2 diabetes, is invalid and unenforceable; Ruling has potential to facilitate launch of a generic repaglinide; Novo Nordisk intends to appeal this ruling;

Patent litigation • Diabetes

REFILE-US top court rules for generic drugmaker on patent (Reuters) - Novo Nordisk's main patent on the drug-Prandin already expired, but it has another that covers the use of repaglinide only when it is used in combination with another diabetes drug, metformin; This patent expires in 2018

Anticipated patent expiry • Diabetes