Effect of SGLT2 inhibitors in People with Advanced CKD with T2D
In a study, initiation of SGLT2i decreased eGFR from 46.1±14.1 to 3.6±13.5 ml/min/1.73m in 1st month in patients with T2D and CKD. Individualized eGFR slopes were improved from -6.4±9.1 to -1.5±3.2ml/min/1.73m/year. Rate of responders: stage 3a (22/29), 3b (22/28), 4 (16/18). Responders were rapid eGFR decliners and had high macro-albuminuria (53% vs 33%)
SGLT2i and GLP-1 RA Use Among US Adults with T2D
How common SGLT2i and GLP1 RA use is among persons with T2D in the US? SGLT2i were used by 7.2% adults with CKD or CHF, and GLP1 RA were used by 3.5% adults with ASCVD. Age, colour & insurance had an impact on medicine use. SGLT2i and GLP1 RA were used less frequently than biguanides, sulfonylureas, DPP-4i, and insulin. From 2013-2014 to 2017-2020, the utilisation of SGLT2i grew dramatically.
Prescribing Patterns of SGLT2 Inhibitors
Clinical trials have shown that adding SGLT2 inhibitors to patients with HF with reduced ejection fraction and HF with preserved ejection fraction, with/without type 2 diabetes, reduces cardiovascular death and HF-related hospitalizations (T2D). Despite guidelines, SGLT2i are underused in patients with HF, with or without T2D. Future research is needed to identify the challenges to adoption.
Stress Hyperglycemia: Independent Marker of Acute Illness
Stress hyperglycemia [inpatient hyperglycemia in patients without known diabetes] is associated with poor outcomes. Stress hyperglycemia is linked to increased prevalence of inpatient CVD, critical illness, organ damage (MI, kidney injury, respiratory failure), and incident DM after discharge. Furthermore, iRPG >140 mg/dl identifies high-risk diabetic patients who should be closely monitored.
Cardiovascular Effectiveness of SGLT2 Inhibitors
SGLT2i lowered the risk of CV events in people with T2D and CVD. Individual SGLT2i did not, however, demonstrate consistent CV improvements in all trials. Dapagliflozin and empagliflozin exhibited similar risks of MI/stroke as canagliflozin, however empagliflozin was linked with a lower risk of HHF. Individual SGLT2i were shown to have a chance of developing additional complications.
SGLT2 Inhibitors Reduce Cardiovascular and Renal Risks
A meta-analysis revealed that SGLT2 inhibitors significantly lowered risks of kidney-specific outcome, MACE and HHF compared to DPP4 inhibitors, and reduced risks of kidney-specific outcome and HHF compared to GLP-1 RAs. GLP-1 RAs also showed cardiovascular and renal outcome benefits compared to placebo. DPP4 inhibitors did not improve either CV or renal outcomes compared to placebo.
24-Hour Plasma FFAs in People with Obesity & Prediabetes
A study meaured plasma FFA concentrations over 24 hours in 20 people with obesity and normal fasting glucose and glucose tolerance (MHO) and 20 adults with prediabetes. It was found that prediabetes group had higher plasma FFA over 24 hours than the MHO group These findings back with the theory that higher 24-hour plasma free fatty acids contribute to obesity-related insulin resistance.
Prevalence of Newly Detected Diabetes
RSSDI data revealed that among people with diabetes, 68669 (87.3%) were on treatment for diabetes. 17646 of them presented in fasting state and 14834 (21.6%) of them had fasting sugar above 130 mg/dl. Out of 42308 diabetic subjects on treatment, 28335 (41.3%) had random blood sugar more than 180 mg/dl. 62.9% of diabetes patients on treatment had their sugar values beyond target range.
The Next Frontier with Dual Incretin
The next generation incretin is a novel GIP and GLP-1 receptor dual agonist. It has been suggested that GLP-1 has dual actions in CNS, islets and stomach. In current research, GIP has shown potential actions in CNS, adipose tissues and islet cells. A single molecule GIP/GLP-1 receptor dual agonist may enable improved physiology greater than the sum of the individual agonist components.
Once-Weekly Insulin Injection - The Future of Diabetes Treatment
A huge step forward in making Type 2 diabetes management easier is on the horizon: the promise of a once-weekly insulin injection. It helps improve adherence, convenience, improve clinical inertia with less missed injections & offer better glycaemic control. However, more data are required on glycaemic control, efficacy & safety, dosing algorithms, post-marketing studies.
Clinical Applications of SLGT-2 Inhibitors
Gliflozins is one of the most important pharmacological interventions of 21st century. Kidney outcomes data now extend across a broad eGFR and UACR range in patients with and without diabetes. Gliflozins forms a key component of “kidney GDMT” towards reducing adverse kidney outcomes.Studies have shown that gliflozin also reduces HF, cardiovascular death, non-fatal MI or stroke.
Holistic Approaches for the Management of Diabetes and CKD
Consensus New Joint Statement from the ADA and KDIGO on Management of Diabetes and CKD: It is crucial to screen for CKD in diabetic patients with eGFR and UACR. Holistic approaches for improving outcomes in patients with diabetes and CKD includes lifestyle and first line therapy - SGLT2i, RASi, metformin and statins. CKA and CVD protection with SGLT-2i and nsMRA and CVD protection with GLP-1 RA.
Definition and Interpretation of Remission in T2D
The potential benefits of coding remission in type 2 diabetes includes removal of personal and social stigmatization as diseased or diabetic; providing a target and a reward for the sustained hard work usually necessary to achieve and maintain substantial weight loss. Diagnosing remission of T2D in the absence of ongoing glucose-lowering medication may enhance the acceptance of a diagnsosis.
New Treatments in Heart Failure With Reduced Ejection Fraction
In the treatment of HFrEF, rapid sequencing should be used instead of conventional sequencing, which involves using a combination of beta-blockers + SGLT2 inhibitors, then progressing to angiotensin receptor neprilysin inhibitors, and finally mineralocorticoid receptor antagonists. All of this should be accomplished within four weeks, and then up titration to target dosages.
Fatty Liver - Risk Factor for Diabetic Neuropathy
People with diabetes, steatosis & fibrosis have common risk factors that drive NAFLD & neuropathy by increasing free fatty acids, altered lipid metabolism that drives lipotoxicity, inflammation & NASH. Hyperglycemia plays a role, but other factors like dyslipidemia, high triglycerides, elevated LDL, reduced HDL & increased free fatty acids play a major role in T2D patients.
Impact of Time In Range(TIR) in Diabetes Management
TIR of 70-180 mg/dL is linked with retinopathy, vascular complications, all-cause and cardiovascular mortality in patient with diabetes. TIR is influential on the quality of life: higher TIR is associated with a more positive mood in people with diabetes and lower ratings with negative mood. International consensus recommends time above range (TAR) >180 mg/dL, and TAR >250 mg/dL in patients.
Emerging Therapies SGLT2-Inhibitors for Treatment of NAFLD
Around 70% of T2D patients have nonalcoholic fatty liver disease (NAFLD). Several studies have shown that the emerging therapies like SGLT-2 inhibitors reduce liver fat, inflammatory markers, Hepatic Steatosis, fibrosis & hepatocellular carcinoma. In a recent study, SGLT-2i has been found to reduce the risk of NAFLD by 36% and it has also reduced transaminase elevation in patients with T2D.
Mitigating ASCVD Risk in Diabetes
The Role of Revascularization in Patients with Diabetes and Chronic Coronary Disease: Revascularization in diabetes with chronic coronary disease lead to 35% reduction in all-cause/CV mortality in the STITCH trial; >35-50% reduction in primary composite and CV death or MI in the ISCHEMIA trial. Revascularization can improve survival in high-risk subgroups such as ischemia and diabetes.
Prevention or Delay of T2D and Associated Comorbidities
ADA 2022 guidelines recommend that individuals with pre-diabetes should be monitored annually for the development of diabetes. They also recommend that adults with overweight/obesity at high risk of type 2 diabetes should be subjected to an intensive lifestyle behavior to achieve and maintain 7% loss of body weight and increase moderate-intensity physical activity to at least 150 min a week.
Individualizing Care Goals for Patients at High Risk of T2D
Individuals with the following criteria should be considered for Diabetes Prevention Program: age ≥25 yrs; high-risk individuals [impaired glucose tolerance 140-199 mg/dl, fasting glucose 95-125 mg/dl, BMI ≥24 kg/m2 (Asians ≥22 kg/m2)]; representation of high-risk racial/ethnic groups. In DPP, patients undergoing lifestyle modifications showed 71% reduction in the incidence of diabetes.
