T2DM

What is the 1st line hypertensive?

ACE-inhibitor, except in people of African or Caribbean family origin, or women for whom there is a possibility of becoming pregnant. If unsucsessful with first-line therapy, add a calcium-channel blocker or a diuretic (usually a thiazide or thiazide-related diuretic). Add the other drug (that is, the calcium-channel blocker or diuretic) if the target is not reached with dual therapy.

What is the target blood pressure of a patient with T2DM?

Add medications if lifestyle advice does not reduce blood pressure to below 140/80 mmHg (below 130/80 mmHg if there is kidney, eye or cerebrovascular damage).

What class of medication is metformin?

Biguanide.

What are the common side effects of metformin?

Common side effects include diarrhea, nausea, abdominal pain and increased lactic acid.

What are the 2 main side effects of SGLT2 inhibitors?

DKA and UTI (due to glycosuria).

What is the effect of metformin?

Decrease hepatic gluconeogenesis. Also increases insulin sensitivity, which increases peripheral glucose uptake.

What is the main action of the glitazones?

Decrease peripheral insulin resistance.

What other medications should be considered if metformin is not tolerated or contraindicated?

Dipeptidyl peptidase-4 (DPP-4) inhibitor or Pioglitazone Sulfonylurea

What dietary advice should be offered to patients with T2DM?

Encourage high-fibre, low-glycaemic-index sources of carbohydrate in the diet, such as fruit, vegetables, wholegrains and pulses; include low-fat dairy products and oily fish; and control the intake of foods containing saturated and trans fatty acids.

List some examples of SGLT2 inhibitors (Hint: -zin).

Examples include canagliflozin, dapagliflozin and empagliflozin

What is the target HbA1c for patients with T2DM?

For adults with type 2 diabetes managed either by lifestyle and diet, or by lifestyle and diet combined with a single drug not associated with hypoglycaemia, support the person to aim for an HbA1c level of 48 mmol/mol (6.5%). For adults on a drug associated with hypoglycaemia, support the person to aim for an HbA1c level of 53 mmol/mol (7.0%).

Give 2 examples of sulfonylureas.

Gliclazide and glimepiride.

What are thiazolidendiones also known as?

Glitazones.

What are some of the potential side effects of sulfonylureas?

Include hypoglycaemia, weight gain and hyponatraemia.

What is the MOA of DPP-4 inhibitors?

Increase incretin levels (GLP-1 and GIP), which inhibit glucagon release, which in turn increases insulin secretion, decreases gastric emptying, and decreases blood glucose levels.

Why are sulfonylureas ineffective in the treatment of T1DM?

Ineffective where there is absolute deficiency of insulin production due to action on pancreatic beta cells.

What is the step-wise management of T2DM?

Initial drug treatment = Treatment with a single non-insulin blood glucose lowering therapy (monotherapy) 1st intensification of drug treatment = Treatment with 2 non-insulin blood glucose lowering therapies in combination (dual therapy) 2nd intensification of drug treatment = Treatment with either 3 non-insulin blood glucose lowering therapies in combination

A 78-year-old man with type 2 diabetes mellitus is reviewed in the diabetes clinic. He is currently taking metformin 1g bd. He also has a history of hypertension and hypothyroidism. His HbA1c one year ago was 44 mmol/mol (6.2%). The most recent test is reported as 46 mmol/mol (6.4%). What is the most appropriate next step in management?

Make no changes This man has acceptable glycaemic control, both in terms of NICE guidance and more recent evidence looking at the harms of overzealous glycaemic control. No changes should therefore be made for now. It's worthwhile thinking of the average patient who is taking metformin for T2DM, you can titrate up metformin and encourage lifestyle changes to aim for a HbA1c of 48 mmol/mol (6.5%), but should only add a second drug if the HbA1c rises to 58 mmol/mol (7.5%)

What is 1st line medication for adults with T2DM?

Metformin

In what situations is metformin contraindicated?

Metformin is contraindicated in people with any condition that could increase the risk of lactic acidosis, including kidney disorders, lung disease and liver disease. Metformin is recommended to be temporarily discontinued before any radiographic study involving iodinated contrast agents, (such as a contrast-enhanced CT scan or angiogram), as the contrast dye may temporarily impair kidney function, indirectly leading to lactic acidosis.

What are the side effects of the gliptins?

Nasopharyngitis, headache, nausea, heart failure, hypersensitivity and skin reactions. They may cause severe joint pain.

In what situations should patients with T2DM be offered self-blood glucose monitors?

Patient on insulin Evidence of hypoglycaemic episodes or on oral medication that increases the risk of hypoglycaemia while operating heavery machinery Pregnant or planning to become pregnant

What is the most common glitazones?

Pioglitazone

A 72-year-old man is reviewed in the diabetes clinic. He has a history of heart failure and type 2 diabetes mellitus. His current medications include furosemide 40mg od, ramipril 10mg od and bisoprolol 5mg od. Clinical examination is unremarkable with no evidence of peripheral oedema, a clear chest and blood pressure of 130/76 mmHg. Recent renal and liver function tests are normal. Which diabetic medications is contraindicated?

Pioglitazone Thiazolidinediones are absolutely contraindicated in heart failure.

What is Type II diabetes?

Relative deficiency of insulin due to an excess of adipose tissue and insulin resistance.

What is the MOA of SGLT2 inhibitors?

Reversibly inhibit sodium-glucose co-transporter 2 (SGLT2) in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion.

Give an example of a DPP-4 inhibitor?

Sitagliptin.

What is the MOA of sulfonylureas?

Sulfonylureas bind to and close ATP-sensitive K+(KATP) channels on the cell membrane of pancreatic beta cells, which depolarizes the cell by preventing potassium from exiting. This depolarization opens voltage-gated Ca2+ channels. The rise in intracellular calcium leads to increased fusion of insulin granulae with the cell membrane, and therefore increased secretion of (pro)insulin

What is the MOA of thiazolidinediones?

Thiazolidinediones are a class of agents used in the treatment of type 2 diabetes mellitus. They are agonists to the PPAR-gamma receptor and reduce peripheral insulin resistance. The PPAR-gamma receptor is an intracellular nuclear receptor. It's natural ligands are free fatty acids and it is thought to control adipocyte differentiation and function.

What are the side effects of the thiazolidinediones?

Weight gain Liver impairment --> monitor LFTs fluid retention (contraindicated in HF) Fractures Bladder cancer

At what eGFR should metformin be stopped?

eGFR < 30 ml/minute/1.73m2.