scholarly journals How Novel is Dapagliflozin?

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A385-A386
Author(s):  
Shyamsunder Vachhani ◽  
Gautam Das
Keyword(s):  
Type 2 Diabetes ◽  
Emergency Department ◽  
Blood Glucose ◽  
Discharge Planning ◽  
Rare Complication ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Anion Gap ◽  
Diabetes Clinic

Abstract Introduction: Dapagliflozin is one of the novel class of glucose-lowering agents known as sodium-glucose co-transporter-2 (SGLT2) inhibitors and is used in the treatment of patients with type 2 diabetes. Diabetes Ketoacidosis (DKA) is defined by the triad of hyperglycaemia, anion-gap acidosis, and increased plasma ketones. Euglycemic DKA is an uncommon form of ketoacidosis which is characterized by metabolic acidosis with a pH <7.3 and a serum bicarbonate of <18mEq/L, ketosis, and a blood glucose level of <200 mg/dl. This can be caused by SGLT2 inhibitors. Euglycemic diabetes ketoacidosis is a rare complication that occurs in patient taking SGLT2 inhibitors. Here we describe a patient with euglycemic DKA. The incidence of DKA associated with dapagliflozin has been reported to be < 0.1%. Case Presentation: This 55 years old gentleman has past medical history of obesity, type 2 diabetes (since age of 27 yrs.), hypercholesterolemia, hypertension and osteoarthritis. He recently suffered from myocardial infarction discharged 2 days back and presented to emergency department with central chest pain radiating to both arms in the morning. ECG reported as normal and venous blood gas showed pH- 7.10, pCo2- 3.84, pO2- 5.54, glucose- 10, lactate-1.8, bicarbonate- 8.5, base excess 19.2, anion gap 25. And dapagliflozin was stopped as a part of discharge planning and followed up in our diabetes clinic. Urine dipstick revealed Glucose +2, ketone +4, pH 5. He was diagnosed to be suffering from euglycemic diabetic ketoacidosis & treated as per protocol. When he recovered from DKA his insulin was optimised and dapagliflozin was stopped as a part of discharge planning and was followed up in our diabetes clinic. Discussion: In patients on dapagliflozin, cases of euglycemic diabetes ketoacidosis are increasingly being reported. Diagnosis of euglycemic diabetes ketoacidosis can be easily missed in the emergency department due to absence of marked hyperglycemia, often leading to delayed diagnosis and treatment. Mechanism of action of dapagliflozin is by selectively inhibiting the transporter protein SGLT2 in the renal proximal, which prevents glucose reabsorption and subsequently induces the elimination of filtered glucose via urine, the process is known as ‘glycuresis’ which reduces the blood glucose levels. SGLT-2 inhibitors should be initiated by a clinician cautiously and only after adequately weighing the risks and benefits of treatment. It is advisable to do urine test on patient taking dapagliflozin on admission which will help diagnose euglycemic DKA early. To prevent this potentially dangerous complication, patients taking SGLT2 inhibitors who become ill should discontinue the medication, undergo ketone evaluation, and start basal insulin, if ketones are positive. In addition, patients should be educated to stop their SGLT2 inhibitor at least 1 week prior to elective procedures.

scholarly journals Euglycemic Diabetic Ketoacidosis Secondary to SGLT2-inhibitor Use in Combination With a Ketogenic Diet

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A380-A381
Author(s):  
Joi C Hester ◽  
Stacy Zimmerman ◽  
Teresa Allison Nimmo ◽  
Wesley Cunningham ◽  
Joshua Liu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Diabetic Ketoacidosis ◽  
Ketogenic Diet ◽  
Sglt2 Inhibitor ◽  
Perioperative Period ◽  
Anion Gap ◽  
Arterial Blood ◽  
Euglycemic Diabetic Ketoacidosis

Abstract Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are cardiorenal protective agents increasingly used in patients with diabetes. Cases of euglycemic diabetic ketoacidosis (euDKA) have been reported particularly among patients with type 1 diabetes. Our case is an example that highlights the role SGLT-2 inhibitors play in the development of euDKA in a patient with type 2 diabetes with confounding factors of strict adherence to a ketogenic diet and ankle fracture. A 72-year-old female with a history of type 2 diabetes presented to the emergency department (ED) with right ankle pain and obvious deformity after a mechanical fall. Radiography of the right lower extremity confirmed distal fracture of the tibia and fibula. After reduction of her fracture in the ED, she was admitted in anticipation of an open reduction internal fixation. Her diabetes was controlled on empagliflozin monotherapy and adhering to a ketogenic diet. She monitored her blood ketones daily at home and reported values in the 3–4 mmol/L range. On admission, her basic metabolic panel (BMP) revealed a blood glucose of 148 mg/dL, bicarbonate of 20 mEq/L, anion gap of 18 mEq/L, Cr of 1.3 mg/dl, and eGFR of 40 mL/min. Her beta-hydroxybutyrate (BHB) was 5.09 mmol/L. The initial assessment was presumed starvation ketosis. On hospital day three, she complained of continued nausea, polydipsia, and abdominal pain. Chart review revealed nocturia with approximately 3–4 voids per night. Repeat BMP showed a blood glucose of 152 mg/dL, bicarbonate of 16 mEq/L, anion gap still at 18 mEq/L, Cr 1.4 mg/dl, and eGFR of 37 mL/min. Since admission, all of her blood glucose levels ranged between 118–178 mg/dL. She denied dyspnea but exhibited Kussmaul respirations on physical exam. Repeat labs revealed a BHB of 8.92 mmol/L, and arterial blood gas (ABG) showed pH 7.2, pCO2 23, pO2 100, bicarbonate 8.6 mEq/L, consistent with high-anion gap metabolic acidosis, confirming the diagnosis of euDKA. Her empagliflozin had been held since admission, but she had not received any insulin up to this point due to euglycemia. She was immediately started on a weight-based dose of 12 units of insulin glargine with subsequent improvement of her BHB and anion gap. This patient’s use of an SGLT2-inhibitor in combination with her being on a ketogenic diet, contributed to a nonregulated state of ketone production leading to euDKA in the perioperative period. As SGLT2-inhibitors become more readily available, it is important to educate physicians and patients about the risk of euDKA during fasting, ketogenic diets, and the perioperative period.

scholarly journals A Case of Euglycemic Diabetic Ketoacidosis Following Canagliflozin Therapy

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A358-A358
Author(s):  
Kubra M Tuna ◽  
Randa Abdelmasih ◽  
Ramy Abdelmaseih ◽  
Mrhaf Alsamman ◽  
Joseph Robbins
Keyword(s):  
Fatty Acid ◽  
Metabolic Acidosis ◽  
Blood Glucose ◽  
Side Effects ◽  
Diabetic Ketoacidosis ◽  
Sglt2 Inhibitor ◽  
Oral Intake ◽  
Sglt2 Inhibitors ◽  
Anion Gap

Abstract Introduction: Diabetic ketoacidosis (DKA) is a life-threatening complication of diabetes mellitus (DM). In general, DKA characterized by blood sugar over 250 mg/dL, anion-gap metabolic acidosis, and increased plasma or urine ketones. Approximately 2–3% of DKA patients can present with normal blood glucose levels (less than 250 mg/dl) which called euglycemic DKA. Some of the etiologies of euglycemic DKA include recent use of insulin, low caloric intake, alcoholism, chronic liver disease, and pregnancy. Very rarely, SGLT2 inhibitor use may be responsible for euglycemic DKA. Case Presentation: Here we present a case of 44 years old female with a past medical history of DM type 2 who presented with acute onset of nausea and vomiting. Initial laboratory findings were remarkable for anion gap metabolic acidosis with a blood glucose level of 201 mg/dl. The patient was on long-acting insulin along with Canagliflozin and Metformin therapy over years and reported being compliant with medications. She was treated with intravenous insulin therapy which resolved acidosis as well as symptoms. The patient was discharged with recommendations of discontinuation of Canagliflozin. Discussion: SGLT2 inhibitors are the novel class of oral antidiabetic drugs which widely used due to their favorable cardiovascular and renal outcomes independent of glycemic control. However, their side effects remain a concern. DKA is a rare but serious side effect of SGLT2 inhibitors with an incidence rate of 9.4% in type 1 DM and less than 0.2% in type 2 DM. Patients typically present with euglycemia or low-grade hyperglycemia which results in a diagnostic challenge for treating physicians. SGLT2 inhibitors increase urinary glucose excretion with a subsequent decrease in circulating insulin and an increase in glucagon, rendering a metabolic shift from glucose to fatty acid utilization. During times of intercurrent illness (decreased oral intake, sepsis) or metabolic stress (surgery), decreased carbohydrate intake coupled with the aforementioned changes will result in decreased insulin secretion and increased counter-regulatory hormones including adrenaline and cortisol, promoting lipolysis, fatty acid oxidation, and ketone production by the liver which ultimately leading to euglycemic DKA. Conclusion: SGLT2 inhibitors induced euglycemic DKA treatment is identical to classic DKA with consideration of the lack of hyperglycemia. Appropriate patient counseling to ensure safe SGLT2 inhibitor therapy is crucial, including appropriate holding parameters during concomitant volume-depleting illnesses and decreased oral intake. Timely diagnosis of euglycemic DKA, and recognitions of other rare but lethal side effects to decrease overall morbidity and mortality.

scholarly journals Impact of sodium–glucose cotransporter 2 inhibitors on renal function in participants with type 2 diabetes and chronic kidney disease with normoalbuminuria

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Akinobu Nakamura ◽  
Hideaki Miyoshi ◽  
Hiraku Kameda ◽  
Kumiko Yamashita ◽  
Yoshio Kurihara
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Creatinine Ratio ◽  
Sodium Glucose Cotransporter ◽  
Clinical Records

Abstract Background We compared the effects of sodium–glucose cotransporter 2 (SGLT2) inhibitors on renal function in participants with type 2 diabetes and chronic kidney disease (CKD) classified by degree of albuminuria. Methods A retrospective review of the clinical records of Japanese participants with type 2 diabetes (age > 20 years; SGLT2 inhibitor treatment > 2 years; estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2) was conducted. Based on the urinary albumin-to-creatinine ratio (UACR) or urinary protein-to-creatinine ratio (UPCR) at the start of SGLT2 inhibitor administration, participants were categorized into three groups: normoalbuminuria (A1; UACR < 30 mg/g Cr or UPCR < 0.15 g/g Cr), microalbuminuria (A2; UACR 30 to < 300 mg/g Cr or UPCR 0.15 to < 0.50 g/g Cr), and macroalbuminuria (A3; UACR ≥ 300 mg/g Cr or UPCR ≥ 0.50 g/g Cr). The study outcome was a comparison of the rates of change in renal function evaluated by eGFR at 2 years after starting SGLT2 inhibitor among the three groups. Results A total of 87 participants (40 females, 47 males) were categorized into three groups: A1 (n = 46), A2 (n = 25), and A3 (n = 16). eGFR was similarly decreased at 2 years before starting SGLT2 inhibitor in all three groups. However, the decline in eGFR was ameliorated at 2 years after starting SGLT2 inhibitor, and eGFR was rather increased in the A1 and A2 groups. Interestingly, the rate of change in eGFR at 2 years after starting SGLT2 inhibitor in the A1 group was significantly higher than that in the A3 group. Conclusions These results demonstrate that more favorable effects of SGLT2 inhibitors on renal function were observed in participants with type 2 diabetes and CKD with normoalbuminuria compared with those with macroalbuminuria. Trial registration UMIN-CTR: UMIN000035263. Registered 15 December 2018

scholarly journals Potential Impact on Lipoprotein Subfractions in Type 2 Diabetes

2019 ◽  
Vol 12 ◽  
pp. 117955141986681 ◽  
Author(s):  
Yuka Kamijo ◽  
Hideto Ishii ◽  
Tomohiko Yamamoto ◽  
Kunihisa Kobayashi ◽  
Hiroyuki Asano ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Sglt2 Inhibitor ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Sglt2 Inhibitors ◽  
Diabetic Patients ◽  
Lipoprotein Subfractions ◽  
Cholesterol Levels

Introduction: Recently, the sodium-glucose cotransporter2 (SGLT2) inhibitor empagliflozin has been shown to lower cardiovascular risk among diabetic patients. It is intriguing that some SGLT2 inhibitors have been found to increase low-density lipoprotein (LDL) cholesterol levels, while the relevance to high-density lipoprotein (HDL) cholesterol is unknown. Although the inhibitory effect of SGLT2 inhibitors on glucose reabsorption may accelerate compensatory lipid metabolism and subsequently reduce body weight and affect the lipid profile, much remains unclear about this mechanism. Therefore, we conducted this study to investigate in detail how canagliflozin affects lipoprotein fractions including LDL and HDL subclasses. Materials and Methods: This study is a multicenter prospective study. The participants were patients with 22 type 2 diabetes (60.7 ± 11.6 years, 59.1% of men) who had HbA1c ⩾ 7.0% and consented to participate in the study. They were administered 100 mg canagliflozin orally once per day. Biochemistry test and cholesterol levels of 20 lipoprotein fractions (G1-G20) using high performance liquid chromatography methods were examined before and after 12 weeks of treatment period. Results: Significant decreases were observed in the participants’ body weight (69.7 to 67.9 kg, P < .001), systolic blood pressure (129.3 to 119.5 mm Hg, P < .01), and HbA1c (8.5% to 7.4%, P < .001). Cholesterol levels in the 20 lipoprotein fractions increased for very large HDL (G14, G15) and large HDL (G16) ( P < .05). Conclusions: Reduction in body weight, improvement of blood glucose levels, and increases in very large HDL and large HDL subclasses were observed after canagliflozin treatment. These beneficial changes might contribute to subsequent suppression of cardiovascular outcomes.

scholarly journals Case Reports That Illustrate the Efficacy of SGLT2 Inhibitors in the Type 1 Diabetic Patient

2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
David S. H. Bell
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Case Reports ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Endogenous Insulin ◽  
Large Randomized Clinical Trial ◽  
Endogenous Insulin Production

SGLT2 inhibitors are only approved for use in adults with type 2 diabetes. However, because SGLT2 inhibitors have a mechanism of action that does not require the presence of endogenous insulin, these drugs should also be efficacious in type 1 diabetes where endogenous insulin production is greatly reduced or absent. Herein, I present five cases which illustrate the benefits of utilizing an SGLT2 inhibitor with type 1 diabetes. In these cases the use of SGLT2 inhibitors resulted not only in better glycemic control in most patients but also in some patients’ less hypoglycemia, weight loss, and decreased doses of insulin. In type 1 diabetesCandida albicansvaginitis and balanitis may occur more frequently than in type 2 diabetes. These cases show that a large randomized clinical trial of SGLT2 inhibitors in type 1 diabetes needs to be performed.

scholarly journals MON-LB119 Euglycemic Diabetic Ketoacidosis in a Patient on Canagliflozin Presenting With Hypoglycemia

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Sindhura Inkollu ◽  
Sindhuja Korem ◽  
Sudha Ganne
Keyword(s):  
Blood Glucose ◽  
Diabetic Ketoacidosis ◽  
Mental Status ◽  
Altered Mental Status ◽  
Sglt2 Inhibitors ◽  
Anion Gap ◽  
Hypoglycemic Agents ◽  
Tract Infections ◽  
Euglycemic Diabetic Ketoacidosis

Abstract Background: Sodium glucose co-transporter 2 (SGLT-2) inhibitors are newer class of antihyperglycemics that cause reversible inhibition of the sodium-glucose cotransporters in the renal proximal tubules resulting in increased urinary glucose. Common side effects include yeast and urinary tract infections. The US Food and Drug Administration issued a safety warning pertaining to the development of diabetic ketoacidosis (DKA) with the use of SGLT2 inhibitors. The mechanisms by which SGLT2 inhibitors cause euglycemic DKA are unclear. SGLT2 inhibitors may lead to a decrease in either endogenous or exogenous insulin and an increase in glucagon production.1 This insulin deficiency or resistance may be mild in Type 2 diabetics, however, preventing the profound spike in blood glucose seen in traditional DKA. Here, we report a case of euglycemic DKA in a patient on Canagliflozin who presented initially with hypoglycemia. Clinical case: A 70 year old female presented with altered mental status for 1 day duration. Her past medical history is significant for type 2 Diabetes Mellitus, being managed on Canagliflozin, Glimepiride and Janumet. One week prior to admission she had lumbar spinal fusion surgery. Since then she has been feeling weak and tired with poor oral intake, but continued to use her medications. Initial laboratory findings showed blood glucose of 68 (70-100 mg/dl) without any acidosis. Her altered mental status was attributed to higher opioid doses which she received prior. Oral hypoglycemic agents have been held. On 2nd day of hospitalization, patient became more lethargic and complained of nausea. Laboratory testing revealed a serum glucose of 250mg/dL, serum bicarbonate of 13 (21–31mmol/L), and Anion gap of 25 (3.6–11.0mmol/L). With the suspicion of DKA, a beta-hydroxy butyrate level was obtained which was elevated at 90.10 (0 – 4.16 mg/dL). Venous blood gas analysis was significant for pH 7.23 (7.31-7.41) and pCO2 – 28 (41-51 mmHg). Urinalysis showed ketosis and glucosuria. Patient was diagnosed as euglycemic diabetic ketoacidosis from Canagliflozin in presence of precipitating factors - stress and poor intake. Patient was treated with insulin drip and intravenous fluids with reduction in anion gap and correction of acidosis within 24hrs. There was a gradual improvement in her mental status. She was discharged on subcutaneous insulin, and all other diabetic medications were stopped. Conclusion: Our case highlights the importance of being vigilant in a patient on Canagliflozin, euglycemic DKA can occur even if they present initially with hypoglycemia and no acidosis. Reference: 1. Ogawa W, Sakaguchi K. Euglycemic diabetic ketoacidosis induced by SGLT2 inhibitors: possible mechanism and contributing factors. J Diabetes Investig. 2016;7(2):135-138.

scholarly journals SGLT2 Inhibitor Induced Euglycemic DKA (EDKA) With Proximal Renal Tubular Acidosis (RTA) as a Rare Fatal Complication in a Non-Insulin Dependent Diabetic Patient: A Challenging Dilemma

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A400-A401
Author(s):  
Randa Abdelmasih ◽  
Ramy Abdelmaseih ◽  
Faysal Rifai ◽  
Elio Paul Monsour ◽  
Justin Reed
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Blood Glucose Level ◽  
Renal Tubular Acidosis ◽  
Anion Gap ◽  
Proximal Renal Tubular Acidosis ◽  
Renal Tubular

Abstract Introduction: Diabetic Ketoacidosis (DKA) is characterized by a triad of hyperglycemia, acidemia, and ketonemia. Rarely, it would present with normal glucose levels making its diagnosis very challenging. The incidence of euglycemic DKA (eDKA) has increased with the introduction of the novel sodium-glucose cotransporter-2 inhibitors (SGLT2i). Currently, the reported incidence of SGLT2i induced DKA is 0.16–0.76 events per 1000 patient-years. We present a rare case of SGLT2i induced eDKA with proximal renal tubular acidosis (RTA). Case Presentation A 69 year-old male with type 2 diabetes mellitus presented to the hospital with severe respiratory distress, nausea and vomiting for 2 days. His home medications include metformin and canagliflozin. He was afebrile with respiratory rate 60 breaths/min. Arterial blood gas: pH 7.21, pCO2 9.2, pO2 223, HCO3 6. Blood glucose level was 120 mg/dl. Urinalysis was positive for large ketonuria &gt;160 mg/dl and glycosuria &gt;500 mg/dl. Serum anion gap and urine anion gap were elevated 29 mEq/L and 105 mEq/L respectively. Serum osmolarity and urine osmolality were elevated 296 mosm/kg and 653 mosm/kg respectively. Lactic acid was 5.3. Acetone was detected in blood. No source of infection was identified. Hemoglobin A1C was 5% and c-peptide was within normal range. Insulin and Islet cells antibodies were negative. DKA protocol was initiated until the anion gap closed. However, non-anion gap metabolic acidosis was persistent with profound hypophosphatemia. Repeat urinalysis showed glycosuria with pH ≤ 5.5, phosphaturia and generalized aminoaciduria. Ultimately, the patient elected to receive hospice care. Discussion: SGLT2i are currently recommended as second-line medications for type 2 diabetes mellitus. Their unique mechanism of action prevents glucose reabsorption from the proximal renal tubules. SGLT2i use is growing significantly, especially after recent clinical trials that demonstrated favorable protective effects. EDKA is precipitated by sepsis, acute illness, dehydration, or starvation. Once the diagnosis is suspected, SGLT2i should be stopped immediately. SGLT2i induced eDKA should be treated in a similar fashion as DKA. It is worth to note that SGLT2i half-life ranges from 11–17 hours, and despite drug discontinuation, glycosuria may persist for several days. What made our case unique and made the diagnosis challenging, was the normal blood glucose level, as well as other differentials that could have easily explained the acidosis including starvation ketosis and lactic acidosis. Also, the state of proximal RTA resembling renal Fanconi syndrome that occurred in correlation with canagliflozin therapy. To the best of our knowledge, this is the fourth reported case of proximal RTA with the use of canagliflozin resulting in life-threatening complications. The diagnosis was very challenging due to lack of awareness of this severe adverse effect.

scholarly journals New SGLT2 inhibitor ertugliflozin: safe and effective in the management of type 2 diabetes

2020 ◽  
pp. 32-41
Author(s):  
V. V. Salukho ◽  
T. A. Ilyinskay
Keyword(s):  
Type 2 Diabetes ◽  
Body Mass ◽  
Clinical Studies ◽  
Sglt2 Inhibitor ◽  
Evidence Base ◽  
Sglt2 Inhibitors ◽  
Adverse Outcomes ◽  
Positive Effects ◽  
Sodium Glucose Cotransporter

Type 2 diabetes mellitus (T2DM) is closely associated with the risk of developing cardiovascular complications. A new approach to treatment of T2DM, based on the inhibition of the sodium-glucose cotransporter type 2 (SGLT2) ensures reliable insulin-independent glycemic control with quick overcome of glucotoxicity, reduction of insulin resistance, and positive effects on body mass, blood pressure and other rates. Besides, pronounces clinical efficacy of SGLT2 inhibitor is marked by its use safety and minimized frequency of adverse events. Along with this, the results of carried-out, randomized clinical studies of cardiovascular safety of different SGLT2 inhibitors showed, that apart from bearing on the risk factors, the inhibition of sodium-glucose cotransporter type 2 leads to cardioand renoprotective effects. In addition, their influence on cardiovascular and renal outcomes is the stronger the more different the pre-existing status of cardiovascular diseases of the patient is, the condition of his renal function and the severity of albuminuria. This article summarizes the main results of carried-out randomized clinical studies of SGLT2 inhibitors, which demonstrate their cardiovascular advantages and compile encouraging results of multicentered studies VERTIS, examining different aspects of the use of the ertugliflazine SGLT2 inhibitor in patients with type 2 diabetes. There is data provided demonstrating a powerful glucoselowering, body-mass lowering and hypotensive impacts of ertugliflazine comparable to the same performance of the best representatives of the class. This article describes an evidence base of the use of the drug in monotherapy and its ability to be combined with other oral hypoglycemic agentsand highlightes a high level of safety of the use of ertugliflazine correspondinding to minimized frequency of adverse outcomes of SGLT2 inhibition and so the potential of SGLT2 inhibitors as a new promising class for the treatment of patients with type 2 diabetes and established cardiovascular disease is revealed.

SGLT2 Inhibitors: A New Generation of Antidiabetic Drugs

2015 ◽  
Vol 8 (2) ◽  
pp. 2787-2798
Author(s):  
S.K Kulkarni ◽  
Madhavi Kuchana ◽  
D Samba Reddy
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Sglt2 Inhibitors ◽  
Antidiabetic Drugs ◽  
New Drugs ◽  
Hypoglycemic Agents ◽  
Great Promise ◽  
Glucose Levels ◽  
Blood Glucose Levels

The incidence of type 2 diabetes is markedly increasing worldwide. Despite a plethora of therapeutic options available for the treatment of type 2 diabetes, the ability to effectively normalize blood glucose levels and prevent    long-term complications of diabetes remains elusive. There is intense search for new drugs for diabetes.  One novel therapeutic class of antidiabetic drugs is sodium-glucose cotransporter 2 (SGLT2) inhibitors. SGLT2 is renal membrane transporter that plays an important role in glucose reabsorption within kidneys. Hence, inhibition of SGLT2 enhances renal glucose excretion, consequently lowers blood glucose levels in an insulin- independent manner. This article describes various SGLT2 inhibitors currently available in the market and also agents that are undergoing clinical trials for the treatment of type 2 diabetes. Currently three SGLT2 inhibitors are approved for clinical use and several others are still in development. The emerging data suggest that SGLT2 inhibitors hold great promise for the clinical management of type 2 diabetes. It remains to be seen whether this class of drugs offers additional advantages over the existing oral hypoglycemic agents.

scholarly journals Once daily administration of the SGLT2 inhibitor, empagliflozin, attenuates markers of renal fibrosis without improving albuminuria in diabetic db/db mice

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Linda A. Gallo ◽  
Micheal S. Ward ◽  
Amelia K. Fotheringham ◽  
Aowen Zhuang ◽  
Danielle J. Borg ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Growth Factor ◽  
Kidney Disease ◽  
Sglt2 Inhibitor ◽  
Collagen Iv ◽  
Daily Administration ◽  
Once Daily ◽  
Glucose Lowering

Abstract Blood glucose control is the primary strategy to prevent complications in diabetes. At the onset of kidney disease, therapies that inhibit components of the renin angiotensin system (RAS) are also indicated, but these approaches are not wholly effective. Here, we show that once daily administration of the novel glucose lowering agent, empagliflozin, an SGLT2 inhibitor which targets the kidney to block glucose reabsorption, has the potential to improve kidney disease in type 2 diabetes. In male db/db mice, a 10-week treatment with empagliflozin attenuated the diabetes-induced upregulation of profibrotic gene markers, fibronectin and transforming-growth-factor-beta. Other molecular (collagen IV and connective tissue growth factor) and histological (tubulointerstitial total collagen and glomerular collagen IV accumulation) benefits were seen upon dual therapy with metformin. Albuminuria, urinary markers of tubule damage (kidney injury molecule-1, KIM-1 and neutrophil gelatinase-associated lipocalin, NGAL), kidney growth, and glomerulosclerosis, however, were not improved with empagliflozin or metformin, and plasma and intra-renal renin activity was enhanced with empagliflozin. In this model, blood glucose lowering with empagliflozin attenuated some molecular and histological markers of fibrosis but, as per treatment with metformin, did not provide complete renoprotection. Further research to refine the treatment regimen in type 2 diabetes and nephropathy is warranted.

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