Medications

What are the Mode of Action, Hypoglycaemia Risk, Dosing, Side Effects, Counselling, Renal Impairment, Hepatic Impairment, Weight Effect for Metformin ?

Medication Group & Drug	Mode of Action	Hypoglycaemia Risk	Dosing	Side Effects	Counselling	Renal Impairment	Hepatic Impairment	Weight Effect
Metformin (Biguanide)	↓ gluconeogenesis so ↓ hepatic glucose production; ↑ peripheral glucose uptake in muscle and adipose; decreases intestinal glucose absorption	Low	500–1000 mg 1–2× daily; max 2 g/day	GI upset, diarrhoea, B12 deficiency, lactic acidosis (rare)	Take with food; GI effects settle; report fatigue (possible B12 issue)	Reduce dose if eGFR <45; avoid <30	Caution due to lactic acidosis risk	Neutral / slight loss

Why is metformin useful in early T2DM?

It works even when β‑cell function is reduced.

What additional metabolic benefits does metformin have?

Improves lipid profile (↓ triglycerides, ↓ LDL)

What conditions other than T2DM can metformin be used for?

Prediabetes, gestational diabetes, PCOS, NA fatty liver disease.

What are the advantages and disadvantages of metformin?

Doesn’t stimulate pancreatic insulin secretion → beneficial when beta cell function is already reduced

What are the Mode of Action, Hypoglycaemia Risk, Dosing, Side Effects, Counselling, Renal Impairment, Hepatic Impairment, Weight Effect for Sulfonylureas?

Medication Group & Drug	Mode of Action	Hypoglycaemia Risk	Dosing	Side Effects	Counselling	Renal Impairment	Hepatic Impairment	Weight Effect
Sulfonylureas (e.g., Gliclazide)	Stimulate pancreatic insulin secretion	High	Once or twice daily	Hypoglycaemia, weight gain	Eat regularly; recognise/treat hypos; avoid skipping meals	Dose reduction often needed	Caution	Gain

What is the main risk of using Sulfonylureas?

Hypoglycaemia

What are the Mode of Action, Hypoglycaemia Risk, Dosing, Side Effects, Counselling, Renal Impairment, Hepatic Impairment, Weight Effect for DPP‑4 inhibitors?

Medication Group & Drug	Mode of Action	Hypoglycaemia Risk	Dosing	Side Effects	Counselling	Renal Impairment	Hepatic Impairment	Weight Effect
DPP‑4 inhibitors (e.g., Sitagliptin)	Prevents breakdown of GLP-1, ↑ incretin, ↑ insulin, ↓ glucagon	Low	Once daily	Headache, nasopharyngitis, pancreatitis (rare)	Report severe abdominal pain	Dose reduction for most except Linagliptin	Generally safe; caution in severe disease	Neutral

What are the advantages and disadvantages of DPP‑4 inhibitors?

Weight‑neutral and low hypoglycaemia risk.

What are the Mode of Action, Hypoglycaemia Risk, Dosing, Side Effects, Counselling, Renal Impairment, Hepatic Impairment, Weight Effect for SGLT2 inhibitors?

Medication Group & Drug	Mode of Action	GLP‑1 RAs (e.g., Semaglutide)	Mimic incretin; slow gastric emptying	Low (unless with insulin/SU)	Weekly or daily injection	Nausea, vomiting, diarrhoea, pancreatitis (rare)	Smaller meals; nausea improves; report abdominal pain	Usually no adjustment; caution if severe	Limited data; caution	Significant loss
Na glucose co-transporter 2 inhibitors (e.g., Empagliflozin, dapagliflozin)	In the PCT it ↑ urinary glucose excretion, decreases plasma glucose control	Low	Once daily T2DM	Genital infections, UTIs, dehydration, DKA (rare)	Hydration; genital hygiene; stop during acute illness	Reduced efficacy at low eGFR; avoid if too low	Generally safe; caution in severe disease	Loss

What are the advantages and disadvantages of SGLT2-inhibitors?

How can GFR levels affect SGLT2 effectiveness?

If GFR < 45 there might be renal impairment glycaemic effects. Should continue to help glucose control

What counselling tips are given to patients on SGLT2?

• Sick day rules as can increase risk of DKA

  • If ill with diarrhoea, vomiting, fever, dehydration then STOP

  • Restart 24hrs after feeling better.

• Keep hydrated by drinking lots of water/fluid

• Stop sglt2 prior to any planned surgery

• Avoid eating very low carb diet/ketogenic diet increased risk of ketosis

What are the Mode of Action, Hypoglycaemia Risk, Dosing, Side Effects, Counselling, Renal Impairment, Hepatic Impairment, Weight Effect for GLP-1 RAs?

Medication Group & Drug	Mode of Action	Hypoglycaemia Risk	Dosing	Side Effects	Counselling	Renal Impairment	Hepatic Impairment	Weight Effect
GLP‑1 RAs (e.g., Semaglutide)	Increases insulin secretion, decreases glucagon and gastric emptying	Low (unless with insulin/SU)	Weekly or daily injection	Nausea, vomiting, diarrhoea, pancreatitis (rare)	Smaller meals; nausea improves; report abdominal pain	Usually no adjustment; caution if severe	Limited data; caution	Significant loss

What are the advantages and disadvantages of GLP-1 receptor agonists?

What are the Mode of Action, Hypoglycaemia Risk, Dosing, Side Effects, Counselling, Renal Impairment, Hepatic Impairment, Weight Effect for insulin? T1DM

Medication Group & Drug	Mode of Action	Hypoglycaemia Risk	Dosing	Side Effects	Counselling	Renal Impairment	Hepatic Impairment	Weight Effect
Replaces/supplements endogenous insulin	High	Individualised; basal/bolus regimens	Hypoglycaemia, weight gain, injection‑site reactions	Hypo recognition; rotate sites; monitor glucose	Lower requirements as renal function declines	May need adjustment	Replaces/supplements endogenous insulin	High

When might insulin be needed in T2DM?

• Severe hyperglycaemia

• Catabolic symptoms

• Failure of oral therapy

• Acute illness or surgery

How do meglitinides work and when are they used?

• Repaglinide

• Stimulate beta cells for rapid, short‑acting insulin release.

• To control post‑prandial glucose spikes

What is the mechanism of Tiazolidinediones and a key ADR?

• Pioglitazone

• Peroxisome Proliferator-Activated Receptor gamma agonists

• Increase insulin sensitivity in muscle, liver, and adipose tissue.

• Fluid retention → risk of heart failure

What are the advantages and disadvantages of Tiazolidinediones?

What are alpha-glucosidase inhibitors?

• Acarbose

• Very rarely used

• Inhibit intestinal alpha-glucosidase in the small intestine.

• Delays breakdown of carbohydrate leading to a slower absorption of glucose.

• Beneficial in reducing post prandial spikes

• Can cause GI side effects

• Contra-indicated in IBD

What is the incretin effect?

• Where oral glucose intake produces a greater insulin response than the same amount of glucose given intravenously, even when blood glucose levels are similar, due to gut hormones.

• Incretin hormone peptides released from the GI tract after food has been ingested.

• These peptides stimulate additional insulin release beyond pancreatic beta cells

• In type 2 diabetes this ‘incretin effect’ is reduced

What are the main incretin hormones?

• GLP-1

• Glucagon dependent insulinotropic polypeptide

GLP agnonists

Resisntant to degradation by DPP4 enzymes that inactivate incretins

How are GLP1s given?

• Subcutaneous injection or oral tablets (semaglutide only). Weekly or daily injection

• Not substitute for insulin. Contra-indicated type 1 diabetes

• Severe and persistent abdominal pain with or without vomiting can be a sign of acute pancreatitis - should be stopped.

• Risk of hypoglycaemia if given alongside insulin and/or SU- monitor closely

• Due to delay in gastric emptying/absorption then can interact with some oral medications

• Extra precaution required with contraception and adjustment of HRT when starting GLP therapy and
  for 4 weeks at every dose change.

• Counselling on missed doses for weekly injections, must have at least 4 day interval between each
  dose

Counselling tips for women on contraception or HRTs

• Incretin based therapy (GLP1 and GIP), delay gastric emptying and may reduce the absorption of any oral form of contraception and HRT.

• FSRH guideline for GLP therapy and contraception:

• All women taking GLP should use contraception

• Those taking tirzepatide (Mounjaro) should switch to a non-oral method or add a barrier method for 4 weeks after initiation and 4 weeks after each dose increase.

• If possible, transfer to transdermal form of delivery

• If not possible double dose of progesterone for 4 week on initiation and every dose increase for 4 weeks

Types of GLP1 drugs