Sodium-glucose cotransporter-2 (SGLT2) inhibitors are filtered and secreted to their primary site of action in the proximal tubule of the kidney. At this site, SGLT2 inhibitors also reduce renal elimination of ketone bodies, a finding implicated in their propensity to cause ketoacidosis. Many commonly used medications have potential to diminish renal elimination of SGLT2 inhibitors and to compound the effects of SGLT2 inhibitors on renal elimination of ketone bodies by inhibiting tubular secretion of the SGLT2 inhibitor itself and/or ketone bodies. We present a case of severe diabetic ketoacidosis (DKA) in a patient with type 2 diabetes occurring several days after co-prescription of empagliflozin and probenecid. Other than the recent introduction of empagliflozin, no cause for the DKA episode was apparent. A pharmacokinetic interaction between probenecid and empagliflozin, involving organic anion transporter 3 (OAT3), reduces proximal tubular secretion of empagliflozin and increases patient exposure to the drug. Whether or not this phenomenon is sufficient to cause severe DKA is discussed. An alternative explanation as to the DKA aetiology is proposed, wherein probenecid may compound effects of empagliflozin on renal elimination of ketone bodies. We suggest that clinicians exercise caution when prescribing SGLT2 inhibitors alongside pharmacologic inhibitors of, or competitors for, proximal tubular organic anion transporters in patients with diabetes mellitus due to the risk of severe DKA.

Sarcopenia is characterized by the progressive loss of muscle mass, strength, and function and poses a significant health challenge among people with diabetes. Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are the backbone of type 2 diabetes treatment. The interplay between SGLT2is and sarcopenia is an area of active research with inconclusive results. This article presents an unexpectedly rapid weight reduction, along with physical performance deterioration, in an elderly patient with type 2 diabetes, which led to treatment discontinuation. A bioelectrical impedance analysis confirmed severe sarcopenia development. Until more data are available, sarcopenia and body composition screening and monitoring may be warranted whenever SGLT2is are prescribed.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) use is associated with an increased risk of diabetic ketoacidosis (DKA). The clinical data regarding the use of SGLT2i and its potential side effects in oncology patients is limited. We are retrospectively reporting four oncology patients with type 2 diabetes mellitus using SGLT2i who were admitted with DKA. The mean age of the patients was 61.25 years, and male to female ratio was 1:1. The duration of type 2 diabetes ranged from 10 to 20 years (mean 15.75 years) and the types of SGLT2i used were empagliflozin 25 mg and dapagliflozin 10 mg. The types of malignancy in our case series included squamous cell carcinoma of the cheek, ovarian cancer, and two patients had laryngeal carcinoma (squamous cell carcinoma). Diabetic ketoacidosis was diagnosed in three patients following chemotherapy or concurrent chemo-radiotherapy. Poor oral intake and infections were the main risk factors in our patients. Mean blood glucose level, anion gap, and bicarbonate level were 11.7 mmol/l, 32.25, and 5 mmol/l, respectively. The majority had moderate DKA based on pH (mean 7.13). The hospital course was complicated by acute kidney injury (n=4), infections (n=4) (urinary tract infections, and pneumonia), and three patients required critical care. The mean length of hospitalization was 19.2 days and no mortality was reported among our patients. SGLT2i-related DKA is an emerging complication recognized in oncology patients. Some of the risk factors for this complication are starvation, poor oral intake, and infection which are quite prevalent in oncology patients. Temporary holding of SGLT2i medication during this period might have a potential preventive role.

OBJECTIVE: To investigate the effect of SGLT2i on the GH/IGF1 axis in male patients with newly diagnosed type 2 diabetes (T2D).
METHODS: Sixty male patients with newly diagnosed T2D were recruited, and randomly assigned to Metformin+SGLT2i group or Metformin group after baseline assessment. All patients received standard lifestyle interventions, and blood indices were obtained before and after 12 weeks of treatment.
RESULTS: After 12 weeks of treatment with Metformin+SGLT2i, there were noteworthy improvements in patients\' FPG (Fasting plasma glucose), HBA1c, HOMA-IR, HOMA-β, TyG (Triglyceride-glucose) index and UACR (P < 0.05). Both IGF1 (P = 0.01) and the IGF1/IGFBP3 ratio (P < 0.01) considerably increased, while GH and IGFBP3 did not show significant changes. When comparing Metformin+SGLT2i group to Metformin group, SGLT2i significantly improved HOMA-IR [P = 0.04], and elevated IGF1/IGFBP3 ratio [P = 0.04], SGLT2i showed a tendency of increasing IGF1 (P = 0.10), but this was not statistically meaningful. There was no effect on GH and IGFBP3. Correlation analysis showed that blood IGF1 was negatively correlated with FPG, HBA1c, HOMA-IR, TyG index and positively correlated with IGFBP3. Regression analysis indicated that FPG and testosterone had a negative effect on blood IGF1 level, while HOMA-IR had no obvious effect.
CONCLUSIONS: In male patients with newly diagnosed T2D, SGLT2i can increase IGF1/IGFBP3 ratio, alleviate insulin resistance, but has no significant effect on GH and IGF1 levels. Additionally, our study showed that Metformin+SGLT2i treatment resulted in an increase in blood IGF1 levels and improved insulin resistance, suggesting a potentially beneficial role of IGF1 in newly diagnosed T2D.

Renal congestion in heart failure (HF) is a predictor of the prognosis of cardiovascular disease. The effect of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and vagus nerve stimulation (VNS) on renal congestion has not been reported in HF. A 77-year-old man with HF with preserved ejection fraction (HFpEF) was referred to our hospital because of poor response to loop diuretics. Echocardiography showed severe tricuspid regurgitation with dilation of the right atrium. Three months after adding SGLT2i, body weight was lost without worsening of renal function. Left and right doppler-derived intrarenal venous flow (IRVF) has been changed from a monophasic to a discontinuous pattern with a systolic interruption. One month later, he discontinued SGLT2i administration at his own discretion. In order to stabilizing autonomic balance, transcutaneous VNS (tVNS) was performed via left ear tragus. One hour after transcutaneous tVNS, ipsilateral IRVF has been dramatically improved from a fusional biphasic to a discontinuous pattern with a systolic interruption. SGLT2i and tVNS may be associated with renal decongestion in HFpEF.

BACKGROUND: Euglycemic diabetic ketoacidosis (DKA) is a potentially life-threatening adverse condition associated with use of sodium-glucose cotransporter-2 inhibitors (SGLT2i). This risk is further pronounced in the perioperative period. There is no consensus for when SGLT2i should be held preoperatively, and recommendations from various organizations have evolved from 1 day to 3 to 4 days in the latest American Diabetes Association guidelines. Further study of patients with perioperative euglycemic DKA is required to help clarify the optimal timing of preoperative discontinuation of SGLT2i agents.
METHODS: In this retrospective, single-centre case series we examined 4 patients who developed postoperative euglycemic DKA after coronary artery bypass grafting, 3 of whom underwent semiurgent surgery. We characterized their clinical course, predisposing factors and treatment characteristics.
RESULTS: The SGLT2i were held for 1 to 5 days preoperatively, with times since last dose before surgery being 54, 79, 80 and 151 hours. Surgery was semiurgent for 3 patients, and elective for 1 patient. Three patients were diagnosed with euglycemic DKA within 24 hours after surgery. The fourth patient developed euglycemic DKA on postoperative day 3 in the context of significant hypovolemia and exhibited potential signs of protracted SGLT2i action at 7 days since the last dose.
CONCLUSIONS: The duration of SGLT2i action and risk for DKA is variable and complex. Providers should hold SGLT2i at least 3 days before elective major surgery, with potentially longer times in high-risk patients. Careful vigilance should be used for perioperative DKA development in all patients recently exposed to SGLT2i.

Immune checkpoint inhibitors (ICIs) have become a new hope for many patients with advanced cancer by blocking tumour immune evasion. However, with the widespread use of ICIs, immune-related adverse events (irAEs) have also been discovered and reported increasingly. Immune-related myocarditis, the most dangerous one of irAEs, still has high mortality in the context of the current treatment. We report the case of a 60-year-old female with fulminant myocarditis induced by ICIs, which caused her to experience frequent ventricular arrhythmias such as ventricular fibrillation and heart failure. She was successfully treated with current mainstream therapies for immune-related myocarditis and additional treatment of sacubitril-valsartan and dapagliflozin. The intriguing observation that the patient condition recovered relatively rapidly in this case shows a possible treatment inspiration, which may be helpful for treating ICIs-associated myocarditis and improving cancer patients\' clinical prognosis.

Diabetic ketoacidosis (DKA), an acute and life-threatening complication of diabetes, is a metabolic disorder caused by insulin deficiency and an increase in counter-regulatory hormones. Several cases of DKA without marked hyperglycemia have been reported and are defined as euglycemic DKA (eu-DKA). The use of sodium-glucose cotransporter 2 inhibitors (SGLT2is) is associated with the occurrence of eu-DKA, of which, dapagliflozin is one of the agents. In this study, we report a case of dapagliflozin-associated eu-DKA following surgery for pancreatic carcinoma. A 57-year-old woman presented with acute abdominal pain after surgery for pancreatic carcinoma. Emergency exploratory laparotomy was performed because of suspicion of gastrointestinal perforation based on a CT scan. The surgeons observed that the stomach was significantly dilated but not perforated. Meanwhile, the patient developed shock and severe acidosis. A further examination confirmed the diagnosis of dapagliflozin-associated eu-DKA. We reviewed the precipitating factors and mechanisms of SGLT2i-associated eu-DKA and discussed the treatment and prevention of this condition. Clinicians need to be alert of the occurrence of SGLT2i-associated eu-DKA in patients treated with this drug in the perioperative period.

Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are novel oral hypoglycaemic agents. For patients with diabetes mellitus, without a prior history of myocardial infarction or atherosclerotic disease, SGLT2i have been shown to reduce incident heart failure and worsening renal function. SGLT2i therapy is increasing among patients presenting for cardiac surgery. However, the perioperative use of SGLT2i carries a significant risk of euglycaemic diabetic ketoacidosis, due to their catabolic mechanism of action. This case report demonstrates euglycaemic ketoacidosis post-coronary artery bypass grafting secondary to SGLT2i, highlighting the multiple risk factors and consequences of this iatrogenic complication.

Diabetes mellitus (DM) represents one of the most frequent comorbidities in patients with acromegaly. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) represent an important class for diabetes management. However, limited data is reported regarding the use of this class in patients with acromegaly and diabetes.
Reporting data regarding patients with acromegaly and diabetes under treatment with SGLT2i.
29 acromegalic patients with diabetes were identified. Treatment with SGLT-2i was documented in nine patients, out of them 5 females and 4 males with a mean age (SD) of 61 ± 12 yr. The mean (SD) duration of treatment with SGLT2i was 27.5 ± 7.3 months. Mean HbA1c before and after SGLT-2i initiation was 8.1 ± 1.1 and 7.0 ± 0.9% respectively. Mean IGF-1 level (SD) before SGLT-2i initiation was 177 ± 68 ng/mL and the mean GH level (SD) was 0.7 ± 0.5 µg/L. All nine patients are still under treatment with SGLT2i and none of them had reported any adverse reaction related to SGLT2i.
The present article provides us for the first time with new data regarding the use of SGLT2i among acromegalic patients with diabetes.