Daplo

1. Does Dapagliflozin cause Hyponatremia?

No, Sodium-Glucose Co-transporter 2 (SGLT2) inhibitors induced natriuresis is transient. There are compensatory mechanisms that increases the re-absorption of NA+ ions at other nephron sites. A new steady state is established by terminating negative NA+ ions and maintaining the balance eventually. (https://diabetes.diabetesjournals.org/content/68/6/1109).

2. With the loss of water and salt, patients can get dehydrated. Does that mean the patient needs to drink more water than the usual?

Treatment with SGLT2 inhibitors leads to dehydration if the water intake is not sufficient. The patient should remain adequately hydrated (not more than normal). SGLT2 inhibitors should be withheld in patients with poor nutritional or hydration status. (https://www.uspharmacist.com/article/benefits-and-complications-of-sodiumglucose-cotransporter-2-inhibitors) (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5812257/).

3. Can Dapagliflozin be given for weight loss under normal circumstances?

Though weight loss is an effect of SGLT2 inhibitors, it is not indicated to use in any weight loss or weight management process. However, when used for the approved indications like T2DM, SGLT2 inhibitors do produce weight loss.

4. Is Dapagliflozin a replacement of a Diuretic drug?

No, Diuretics may have only diuretic activity. Apart from their diuretic activity, SGLT2 inhibitors protect the kidney by reducing the rate at which eGFR declines in patients with diabetic nephropathy. In addition to their diuretic activity, DAPA also improves Glycemic control and long-term CV or renal outcomes.

5. How is DAPA superior to other gliflozins?

Unlike other SGLT2 inhibitors, DAPA is supported with data in T2DM patients (DECLARE TIMI) with multiple risk factors (primary prevention population). So, it is the ideal choice in the case of T2DM patients with multiple CV risk factors. DAPA is also well studied for use and fit for use in HF patients with reduced ejection fraction (HFrEF). It can also be used in non-diabetic patients for CV & renal (DAPA CKD) protection.

6. Can DAPA be prescribed to kidney impaired patients?

Yes, it can be prescribed to kidney-impaired patients. Whether the patient is suitable for SGLT2 inhibitors, is decided based on the renal function (eGFR)/stage of CKD. DAPA should not be initiated in patients with a GFR < 60 mL/min. In case the patient is already on DAPA, it should be discontinued, if GFR is persistently below 45 mL/min. DAPA is contraindicated if eGFR is less than 30 mL/min.

7. Can DAPA be used in early Diabetes?

Yes, DAPA can be given in early diabetes. It can be used for initial monotherapy or initial combination therapy. DAPA, especially in those with ASCVD/HF/CKD, will have better CV & renal outcomes when initiated early.

8. Since higher Glucose excretion is through the urine, will it increase the risk of a UTI?

Increased incidence of UTI is a known side effect of SGLT2 inhibitors. However, not everyone will develop UTIs. The incidence of UTIs with DAPA varies from 1.5% in DECLARE TIMI (incidence of UTIs with Placebo was 1.6%) to 5.7% in pooled studies. Meta-analysis of trials and a large population-based cohort study have shown no increased risk, which provides important reassurance for patients and prescribers. (https://www.nature.com/articles/s41574-019-0275-6).  Meta-analysis of randomized controlled trials (RCTs) showed no significant difference in UTIs between SGLT2 inhibitors versus Control. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5460243/).

9. In case of CKD patients, till what stage can we continue prescribing DAPA?

DAPA should not be initiated in patients with a GFR < 60mL/min. In case the patient is already on DAPA, it should be discontinued if the GFR is persistently below 45 mL/min. DAPA is contraindicated if eGFR is less than 30 mL/min.

10. How far can we predict the chances of Urinary Tract Infections?

The incidence of UTIs with DAPA varies from 1.5% in DECLARE TIMI (incidence of UTIs with placebo was 1.6%) to 5.7% in pooled studies.

11. What gives DAPLO an edge over other gliflozins?

Unlike other SGLT2 inhibitors, DAPA is supported with research studies in T2DM patients (DECLARE TIMI) with multiple risk factors (primary prevention population). So, it is the ideal choice in the case of T2DM patients with multiple CV risk factors. DAPA is supported with studies and fit for use in HF patients with reduced ejection fraction (HFrEF). DAPA is supported with studies and fit for use even in non-diabetic patients for CV & renal (DAPA CKD) protection that it offers.

12. Are 5mg and 10mg doses safe for CKD patients?

Yes, for Glycemic control in T2DM patients with CKD, 5mg can be given. In case, DAPA is being prescribed for benefits beyond Glycemic control (CV & renal protection), which is the practice, 10mg must be given (DAPA CKD trial).

13. A common adverse effect of Gliflozin is Ketoacidosis. What about the effect of Daplo?

The incidence of Diabetic Ketoacidosis with DAPA in DECLARE TIMI, was 0.3%. In this case, initiating DAPA is recommended to prevent flaring up of the infection.

14. Is DAPA safe for use in dialysis patients?

DAPA is not approved for use in dialysis patients.

15. Is DAPA safe for Liver Cirrhosis patients with Diabetes?

No, dose modification is needed in mild, moderate, and severe hepatic impairment. However, in severe cases, it should be individually assessed as there are no studies in such a population.

16. Can Daplo be used in non-diabetes obese patients since it shows weight loss?

Though weight loss is an effect of SGLT2 inhibitors, it is not indicated to use in any weight loss or weight management process. However, when used for the approved indications like T2DM, SGLT2Is does result in weight loss.

17. If Daplo lowers systolic pressure, then can we reduce the dependency on ARB?

DAPA is not a substitute for anti-hypertensive agents. The decision to modify the ARBs/anti-hypertensive dose should be taken on a case-to-case basis, based on the individual BP goals.

18. Glycosuria may result in frequent UTIs. Hence, will this increase the cost of therapy as QOL?

A T2DM patient is already at a higher risk of UTI. Though the risk of UTI is increased by SGLT2Is, UTIs can be managed in most cases through early detection and appropriate treatment (along with health & hygiene), which may cost less than treating long-term CV & renal complications of T2DM. At the same time, SGLT2Is offer several benefits beyond Glycemic control, which in the long run improve the QOL. Dapagliflozin showed a more favorable benefit on Japanese T2DM patients’ QOL vs DPP4is (https://link.springer.com/article/10.1007/s13300-020-00941-8). Dapagliflozin improved symptoms, physical function, and quality of life in patients with heart failure and reduced ejection fraction (https://pubmed.ncbi.nlm.nih.gov/31736335/).

19. What are the advantages of SGLT2Is?

SGLT2 inhibitors have a low risk of Hypoglycemia, weight loss, decrease in BP & other benefits beyond Glycemic control (CV & renal protection).

20. According to ADA 2020 guidelines, which class of drugs are recommended in ASCVD/CKD/HF patients as first add on?

Sodium-glucose Cotransporter2 (SGLT2) inhibitors are recommended in ASCVD/CKD/HF patients as first add on.

21. What is the t1/2 of DAPA?

9 hours is considered as half-life of DAPA.

22. Can DAPA be taken with or without food (irrespective of meal)?

Yes, it can be taken with or without food.

23. For which disease conditions is DAPA approved?

DAPA is approved only in T2DM and heart failure.

24. What is the DAPA dosage for glycemic control in T2DM?

The dosage is 5mg or 10mg OD.