The tides, gliptins and gliflozins

 


    Weight loss                              +                            +++                          None

⬇ CVD  Mortality                     +                               +                            None

⬇ MI / Stroke                         None                            +                            None

⬇ CKD progression/Htn          +                             None                        None

⬇HbA1c                                  0.5-0.7                     0.5-1.5                        0.5-0.8



GLP-1 analogues

Mechanism of Action – 
1) Decrease Glucagon secretion
Usually in DM2, in addition to Beta cells (insulin), there is Alpha cell dysfunction as well, which leads to dysregulated glucagon secretion post prandially in diabetics, worsening hyperglycemia. GLP-1 agonists BLUNT glucagon secretion, thereby restoring glucagon levels


2) Increase Glucose mediated insulin secretion – insulin is secreted only in presence of hyperglycemia, thereby making hypoglycemia extremely unlikely


3) Delayed Gastric emptying

There is lack of first phase insulin (pre-formed insulin) in diabetics, therefore, in people eating high glycemic index diet (or simple sugars), leads to hyperglycemia. Delayed gastric emptying reduces sugar absorption

4) Improve satiety (independent of nausea)


GLP1 (tides) have efficacy in weight loss, improving HbA1c and improving vascular plaque related adverse outcomes such as stroke and CAD. 

They have a role in cardiovascular prevention even in non-diabetics. 

HbA1c improvement in order of 0.5 – 1.5

  • Side effects of GLP1 – is mostly gastrointestinal – Nausea, fullness and diarrhoea
..............................................................................................................................................................

DPP4 inhibtors

DPP4 inhibitors – (gliptins) do not have any cardiovascular protective effects, and are weight neutral. They are useful in glycemic control but can cause pancreatitis. 

HbA1c improvement in order of 0.5 – 0.8. 

There is small risk of pancreatitis with DPP4 / GLP-1 analogues – probably not more than baseline risk – and this space continues to be watched for more data and clarity. For now, be suspicious of GLP / DPP4 drugs and their association with acute pancreatitis

-----------------------------------------------------------------------------------------------------------------------

SGLT2 inhibitors

SGLT2 inhibitors (flozins) on the other hand, retard renal deterioration in CKD (diabetics and non-diabetics), improve pump function (CHF) and blood pressure. 

Their hypoglycemic effect, weight loss effect and cardiovascular protective effect is not as marked as GLP1. 

HbA1c improvement in order of 0.5 – 0.7.  

  • Genito-urinary infections, Fractures and Diabetic Ketoacidosis. 
  • SGLT2 inhibitors must be with-held for 3-4 days in case of fasting pre-procedure.

Source: UTD, https://www.youtube.com/watch?v=v6NCRUfeW2A


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