Type	Initial Treatment	Key Considerations	Escalation Criteria
Type 1 Diabetes Mellitus (T1DM)	✅ Insulin therapy immediately: • Basal-bolus regimen (MDI) OR • Continuous subcutaneous insulin infusion (CSII)	• Lifelong insulin dependency • Education on carbohydrate counting, BGL monitoring, ketone testing • CGM or flash glucose monitoring recommended • Refer to diabetes educator and endocrinologist	• Adjust dose based on SMBG/CGM • Consider adjuncts (e.g., SGLT2i in adults only with caution: ↑ DKA risk)
Latent Autoimmune Diabetes in Adults (LADA)	❌ Avoid sulfonylureas ✅ Start metformin if mild hyperglycaemia and insulin still preserved ✅ Early transition to insulin	• GAD/IA-2 antibody positive • Often lean, rapid failure of oral agents • May initially mimic T2DM	• Usually need insulin within 6–24 months • Monitor C-peptide levels if uncertain
Type 2 Diabetes Mellitus (T2DM)	✅ Lifestyle + Metformin (first-line) ✅ Add SGLT2i or GLP-1 RA if: – High CVD risk – CKD – Heart failure	• Weight, renal function (eGFR), cardiovascular risk, hypoglycaemia risk guide drug selection • Early combination therapy if HbA1c ≥1.5% above target	• Escalate to dual/triple therapy (e.g. metformin + SGLT2i + DPP-4i) • Add insulin if HbA1c uncontrolled despite maximal oral/GLP-1 therapy
Monogenic Diabetes (e.g. MODY)	⚠️ Do not assume need for insulin ✅ Sulfonylureas (esp. HNF1A-MODY) ✅ No treatment in GCK-MODY	• Suspect in non-obese patient <25 yrs with strong family history • Refer for genetic testing	• Refer to endocrinologist for subtype-specific therapy • May require insulin if subtype not identified or fails sulfonylurea
Gestational Diabetes Mellitus (GDM)	✅ Lifestyle changes (diet + activity) ✅ Start insulin if: – Fasting BGL ≥5.5 mmol/L – 2-hr postprandial ≥6.7 mmol/L ✅ Metformin may be considered (after counselling; crosses placenta)	• Regular BGL monitoring (QID) • Input from endocrinologist or diabetes educator • Early postpartum OGTT	• Insulin preferred if >30 weeks and suboptimal control • Reassess postpartum for T2DM risk
Steroid- or Medication-Induced Diabetes	✅ Insulin if marked hyperglycaemia ✅ Metformin if appropriate and expected to continue meds long-term	• BGL pattern (e.g., postprandial spikes with prednisolone) • Monitor for hypoglycaemia if steroids tapered	• Re-evaluate need for ongoing therapy after cessation of causative drug • Consider long-term monitoring for T2DM

Notes on Initiation Thresholds (Australian Guidelines):

Initiate pharmacologic treatment if HbA1c >6.5–7% depending on patient profile
Consider early insulin in:
- Marked hyperglycaemia (HbA1c >9%)
- Symptomatic hyperglycaemia
- Ketosis or weight loss
Individualise targets based on:
- Age, comorbidities, risk of hypoglycaemia
- Pregnancy status
- CVD/renal status

The criteria for the diagnosis of diabetes are now:

HbA1c ≥6.5% (48 mmol/mol)
Fasting glucose ≥7.0 mmol/L
Random glucose ≥11.1 mmol/L
On a 75 g oral glucose tolerance test: fasting glucose ≥7.0 mmol/L or 2 hr glucose ≥11.1 mmol/L

https://www.diabetessociety.com.au/guideline/hba1c-for-diagnosis-of-diabetes-mellitus-may-2023

In an asymptomatic patient the test should be repeated for confirmation of the result and diagnosis. An abnormal result on 2 different diagnostic tests is also acceptable

Treatment Algorithm Overview-for Type 2 Diabetes

https://www.diabetessociety.com.au/wp-content/uploads/2023/03/ADS_POSITION-STATEMENT_v2.4.pdf

All patients should receive education on lifestyle measures, including:

Healthy diet
Physical activity
Weight management

Rationale for Treatment:

Prompt management of symptoms related to hyperglycaemia is essential, including acute or chronic symptoms such as fatigue, polyuria, vision disturbances, muscle cramps, and urinary incontinence in cognitively impaired patients.
In severe cases, hyperglycaemia can lead to coma, requiring emergency treatment.
Insulin therapy is highly effective for rapid reduction of high blood glucose levels, especially in symptomatic hyperglycaemia.

HbA1c Target:

Determine the individual’s HbA1c target, commonly ≤53 mmol/mol (7.0%).
Regularly review the target based on individual circumstances.

Therapy Review Timeline:

Review the effects of any changes in therapy within 3 months.

Algorithm for Suboptimal HbA1c:

If HbA1c is not at target, proceed with the following steps:
1. Review Current Therapies: Assess the current treatment regimen.
2. Assess Medication Adherence: Evaluate how consistently the patient is taking their medications.
3. Monitor for Side Effects: Check if any side effects from medications are impacting adherence or effectiveness.
4. Consider Comorbidities: Exclude other comorbidities or therapies that may affect glycaemic control.
5. Evaluate Patient Understanding: Ensure the patient understands their treatment plan and is capable of self-managing their condition.

First-Line Treatment

Lifestyle Modifications (foundation at all stages):

Diet: reduce energy intake, focus on low-GI carbs, increase vegetables and fibre.
Physical activity: minimum 150 minutes/week moderate-intensity aerobic activity.
Weight management: support weight loss or prevent further weight gain.
Reinforce lifestyle changes regularly.

Pharmacotherapy Initiation:

Start Metformin unless contraindicated.
- Mechanism: insulin sensitiser.
- Benefits: weight neutral or modest loss, no hypoglycaemia.
Consider Sulfonylurea if:
- Metformin not tolerated or contraindicated.
Other options:
- Acarbose (PBS subsidised as monotherapy)
- Insulin (consider early if marked hyperglycaemia or catabolic symptoms)
- Non-subsidised: SGLT2i, DPP-4i, GLP-1RA (not for monotherapy under PBS)
Metformin can also be used in LADA – Only if residual β-cell function present – Stop when insulin needed

Second-Line Treatment

When:

Inadequate glycaemic control on metformin alone.

Options (add to metformin or replace sulfonylurea if needed):

Drug Class	Notes
Sulfonylureas	Inexpensive, effective but risk of hypoglycaemia and weight gain.
DPP-4 Inhibitors	Weight neutral low risk of hypoglycaemia PBS subsidised with metformin.
SGLT2 Inhibitors	Weight loss BP reduction PBS subsidised with metformin or sulfonylurea.
Acarbose	Targets postprandial hyperglycaemia modest efficacy GI side effects.
TZDs (e.g., pioglitazone)	Can be used in insulin resistance; weight gain, oedema; PBS available.
GLP-1 Receptor Agonists	Injectable weight loss BP reduction not PBS subsidised with – SGLT2i – DPP-4i combo.
Insulin	Consider especially if HbA1c > 75 mmol/mol (>9%) or symptoms of catabolism. Basal preferred initially; later intensification with bolus possible

📌 Choice should be individualised based on:

Weight issues
Risk of hypoglycaemia
Comorbidities (CVD, renal disease)
Cost/PBS subsidy
Patient preference (oral vs injection)

Third-Line Treatment

Consider triple oral therapy or addition of injectables (GLP-1 RA or insulin).
Always continue metformin (if tolerated).
Cease ineffective agents.
Tailor treatment to:
- HbA1c target
- Weight
- Hypoglycaemia risk
- Comorbidities (e.g. ASCVD, HF, CKD)
- PBS subsidy
- Patient preferences

🔹 TRIPLE ORAL THERAPY

Combination	HbA1c ↓	Key Features	PBS Caveats	Brand Names
Metformin + Sulfonylurea + DPP-4 Inhibitor	↓ 0.6–0.9%	Mild weight gain ↑ hypoglycaemia (~10%)	✅ Subsidised if all 3 agents used together	Sitagliptin (Januvia), Vildagliptin (Galvus), Linagliptin (Trajenta), Saxagliptin (Onglyza)
Metformin + Sulfonylurea + TZD (Pioglitazone)	↓ ~1.0%	↑ weight (3–5kg), oedema ↑ hypoglycaemia (>20%)	✅ Only pioglitazone PBS-listed	Pioglitazone (Actos, generics)
Metformin + Sulfonylurea + SGLT2 Inhibitor	↓ 1.0%	↓ weight ↓ BP similar hypoglycaemia to DPP-4i	✅ Dapagliflozin & Empagliflozin PBS-listed for triple therapy	Dapagliflozin (Forxiga), Empagliflozin (Jardiance)
Metformin + Sulfonylurea + Acarbose	↓ 1.4%	↓ weight (~1.9kg) GI side effects	✅ PBS listed	Acarbose (Glucobay)

GLP-1RA + DPP-4i – Not recommended together (redundant mechanism)

📊 Combination Therapy Matrix (with PBS Criteria)

Medication	Monotherapy	Dual Therapy<br>(Metformin or Sulfonylurea)	Triple Therapy<br>(Metformin + Sulfonylurea)	With Insulin	PBS Criteria
Metformin	✅ Yes	✅ Yes	✅ Yes	✅ Yes	Unrestricted for T2DM
Sulfonylurea	✅ Yes	✅ Yes	✅ Yes	✅ Yes	Unrestricted for T2DM
Insulin	✅ Yes	✅ Yes	✅ Yes	—	PBS available for T2DM (≥1 agent failed)
DPP-4 Inhibitors (e.g., Sitagliptin, Saxagliptin, Alogliptin, Linagliptin)	❌ No	✅ Yes *	❌ No	✅** (Linagliptin only)	Subsidised only for use in dual therapy (with metformin or SU) where one is contraindicated
Pioglitazone	❌ No	✅ Yes *	✅ Yes	✅ Yes	Only approved if metformin/SU not tolerated or contraindicated
Acarbose	✅ Yes	✅ Yes	✅ Yes	✅ Yes	PBS listed for dual/triple therapy where others are contraindicated
Exenatide (GLP-1 RA)	❌ No	✅ Yes *	✅ Yes	❌ Limited use**	PBS listed only if BMI ≥35 AND HbA1c remains >7% despite triple OHA therapy

* Dual/triple therapy permitted only when metformin or sulfonylurea is contraindicated or not tolerated

** Limited PBS coverage for GLP-1 RA and DPP-4i with insulin; PBS only subsidises Linagliptin with insulin due to non-renal clearance

🔷 Parenteral Therapy Options in T2DM/Intensifying therapy

1 GLP-1 Receptor Agonists (GLP-1 RAs)

Key point	Details
When to add	• HbA1c remains above target despite max-tolerated metformin ± sulfonylurea (SU). • Patient has tried – or cannot use – an SGLT2-i. PBS
Glycaemic effect	↓ HbA1c ≈ 0.9–1.2 % (≈ 10–13 mmol/mol) on diabetes doses.
Weight	Mean –2 to –4 kg at 6-12 months (greater with semaglutide).
Practical tips	• Halve the SU dose when you start the GLP-1 RA; up-titrate later only if needed. • Warn about transient GI effects (nausea, vomiting, early satiety).
PBS-subsidised use of semaglutide (Ozempic®)	Dual therapy • with metformin when SU contraindicated/intolerant. • with an SU when metformin contraindicated/intolerant. Triple therapy • metformin + SU + semaglutide. With insulin • Insulin + metformin ± SU + semaglutide are PBS-listed. • Insulin + semaglutide alone allowed only if metformin is contraindicated/not tolerated. Prohibited PBS combinations: any concomitant SGLT2-i, DPP-4 i or another GLP-1 RA. PBS

2 Insulin Therapy

When to consider

Any time glycaemic or clinical status dictates, but especially if:

HbA1c > 75 mmol/mol (9 %) despite optimised non-insulin therapy
Catabolic symptoms (unintentional weight loss, fatigue)
Contraindications/intolerance to oral/GLP-1 RA agents
Acute illness, hospitalisation or peri-operative need

Initiation options

Regimen	Description	Typical starting dose	Key comments
Basal only	NPH or long-acting analogue OD	0.1–0.2 U/kg OD	Preferred first step; continue metformin ± other orals
Premixed OD/BID	70/30 human mix or analogue biphasic	10 U with evening meal (OD) or 6 U BID	Simple for fixed meal patterns
Basal–bolus	Basal OD + rapid-acting each meal	Basal 0.2 U/kg + 4 U per meal	For highly elevated HbA1c or variable meals
CSII (pump)	Continuous sub-Q infusion	Individualised	Rare in T2DM; consider in extreme insulin resistance

3 Continuing / Stopping other agents once insulin is added

Class	Keep with insulin? (PBS)	Rationale & notes
Metformin	✅ Yes (always)	↓ insulin resistance, mitigates weight gain. Cease if eGFR < 30 mL/min/1.73 m².
Sulfonylurea	⚠️ Generally stop or down-titrate	Adds little once basal dose ≥ 0.5 U/kg and ↑ hypoglycaemia risk.
DPP-4 i	✅ Yes	HbA1c –0.6 %, weight-neutral, low hypo risk. Convenient FDCs with metformin.
SGLT2-i	✅ Yes	Weight/BP benefits; cardio-renal protection. Monitor for genital infections & ketoacidosis (keep basal doses moderate).
GLP-1 RA	✅ Yes (exenatide, semaglutide, liraglutide, dulaglutide all PBS-listed with insulin if other PBS criteria met)	Further HbA1c –0.8-1.5 %; significant weight/BP reduction. Teach GI side-effect management.

Common pitfall: Older summaries stated “only exenatide can be PBS-subsidised with insulin”.
Current rule (since Jun 2024) allows any PBS-listed GLP-1 RA with insulin, provided the SGLT2-i step-before criterion is met and no SGLT2-i/DPP-4 i is being claimed concurrently. PBS

Practical sequencing algorithm

Optimise metformin → add SU or SGLT2-i as per guidelines.
If SGLT2-i contraindicated or fails, consider GLP-1 RA (triple with metformin ± SU, or dual if one agent not tolerated).
Persistently high HbA1c or catabolic signs → add basal insulin, continue metformin ± SGLT2-i ± GLP-1 RA; drop SU if hypoglycaemia emerges.
Escalate to premix or basal-bolus if HbA1c still above personalised target.

Always confirm latest PBS item codes and restriction wording before prescribing, as updates occur every cycle.

Additional practical considerations for intensifying therapy in T2DM

4 Self-monitoring of blood glucose (SMBG)

When: Daily during insulin initiation and any period of dose adjustment; at least before breakfast and occasionally at other times (e.g. before main evening meal, 2 h post-prandial, bedtime).
Why:
- Detect and prevent hypoglycaemia, especially when insulin or an SU is on board.
- Provide objective data for dose titration of basal insulin and for deciding whether prandial coverage is required.

5 Insulin titration & review

Step	Practical rule of thumb
Start low	Basal insulin 10 U once daily or 0.1–0.2 U/kg/day if markedly hyperglycaemic.
Adjust every 2–3 days	↑ by 2 U (or 10 %) if the mean of the last 2–3 fasting SMBG readings is above the individual target.
Target	Fasting BGL ≈ 6–8 mmol/L for many adults; personalise for frailty, CVD, pregnancy, etc.
Review at 3 months	• HbA1c still above goal? Check adherence, injection technique, inter-current steroids/illness. • If fasting control is on target but HbA1c remains high, consider daytime hyperglycaemia → add GLP-1 RA or transition to premix/basal–bolus as appropriate.

6 Ongoing treatment adjustments

Before moving to full basal–bolus
Add a GLP-1 RA to basal insulin: improves HbA1c another ~1 %, lowers weight, and cuts hypo risk versus prandial insulin escalation.
If further HbA1c reduction still required
Consider oral adjuncts based on co-morbidities and renal function:
- SGLT2-i: cardio-renal benefit, weight/BP lowering; monitor for euglycaemic DKA if insulin doses get very low.
- DPP-4 i: modest extra HbA1c drop, weight-neutral; useful if GI intolerance to GLP-1 RA.

7 Patient education essentials

Topic	Core messages
Injection technique	Correct pen handling, site rotation, disposal of sharps, storage (2–8 °C until first use, then room temp ≤ 28 days for most pens).
Sick-day management	Never stop basal insulin; check BGLs (and ketones if on SGLT2-i or very insulin-deficient) every 2–4 h; maintain hydration; have an action plan for rising ketones or persistent hyperglycaemia.
Hypoglycaemia awareness	Teach early symptoms (sweats, tremor, confusion) and the 15 g rapid-acting carbohydrate rule; ensure access to glucagon rescue if high risk.
Self-efficacy	Encourage keeping a glucose/insulin diary or using app-based logging to facilitate shared decision-making at each follow-up review.

Glucose-Lowering Therapy in Renal, Hepatic Impairment, and the Elderly

1. Chronic Kidney Disease (CKD)

Pathophysiological Considerations in CKD (especially stages 4–5):

↓ Renal gluconeogenesis → impaired glucose homeostasis.
↑ Insulin resistance due to uraemic toxins and counter-regulatory hormones.
↓ Insulin clearance → prolonged insulin action, ↑ hypoglycaemia risk.
Altered metabolism of glucose-lowering drugs.
Associated abnormalities: dyslipidaemia, acidosis, electrolyte imbalance.

Therapeutic Recommendations:

Drug Class	Considerations	CKD Use
Metformin	Contraindicated if eGFR <30 mL/min/1.73 m² due to lactic acidosis risk	Reduce dose or avoid in stage 4–5
Sulfonylureas	Risk of hypoglycaemia due to reduced renal clearance	Prefer glipizide or gliclazide (shorter acting); avoid glibenclamide
DPP-4 Inhibitors	Require dose adjustment (except linagliptin)	Linagliptin: No adjustment even in dialysis
SGLT2 Inhibitors	Renoprotective effects; limited glycaemic benefit in advanced CKD	Dapagliflozin, empagliflozin OK if eGFR ≥25–30
Insulin	Clearance reduced → prolonged action	Start with lower doses; titrate carefully

🔎 Monitor renal function regularly; adjust therapy based on eGFR and clinical response.

2. Liver Disease

Pharmacokinetic/Metabolic Considerations:

↓ Hepatic gluconeogenesis and glycogenolysis → ↑ hypoglycaemia risk.
↓ Drug metabolism → accumulation of hepatically cleared agents.
Risk of lactic acidosis with hepatic dysfunction.

Therapeutic Considerations:

Drug Class	Use in Mild–Moderate Hepatic Impairment	Notes
Metformin	Generally safe; caution in advanced liver disease	Monitor for lactic acidosis
Sulfonylureas	Use with caution; ↑ hypoglycaemia risk	Prefer short-acting agents
Acarbose	May be used cautiously	Minimal systemic absorption
DPP-4 Inhibitors	Mostly safe	Dose reduction for some (except linagliptin)
TZDs	Use cautiously; avoid in ALT >2.5x ULN	Hepatotoxicity risk
Insulin	Preferred if oral agents contraindicated	Risk of hypoglycaemia ↑

⚠️ Avoid hepatotoxic drugs in cirrhosis or active liver inflammation.

3. Elderly Patients

Key Principles:

Individualise glycaemic targets: Looser goals (e.g., HbA1c ≤64 mmol/mol or ≤8.0%) may be more appropriate in frail or comorbid patients.
Avoid overtreatment: Balance between hyperglycaemia symptoms and hypoglycaemia risk.

Clinical Considerations:

Renal function estimation (eGFR) is more reliable than serum creatinine alone.
Cardiac dysfunction (e.g., heart failure) increases the risk with some drugs (e.g., metformin).
Polypharmacy is common — regular medication reviews are essential.
Minimise hypoglycaemia risk: Prefer agents with low hypoglycaemia potential (e.g., DPP-4 inhibitors, SGLT2 inhibitors, low-dose insulin with careful titration).

🎯 Goals: Maintain functional independence, minimise adverse effects, prioritise quality of life.

MEDICATIONS

Class			HbA1c reduction	Benefits	Adverse effects	Contraindications /Precautions
Biguanides – 🡫 hepatic glucose output – 🡫 insulin resistance	Active ingredients	Brand name(s)^a	1-2%		GIT symptoms (N/V, anorexia, diar, abdo cramps) Lactic Acidosis (cease 48hrs before surgery or contrast radiography)	Avoid if eGFR<30. Caution if eGFR<45, or variable and therefore at risk of decompensation. Advise all patients to stop metformin temporarily if vomiting/diarrhoea, or other risk of acute renal impairment
	Metformin	Diaformin Formet Glucobete Diabex
	Metformin XR	Diaformin XR Metex XR Diabex XR
Sulfonylureas – Improves microvascular complications – 🡩 insulin secretion – max 120mg daily	Glibenclamide	Daonil	0.5–1.3%	Nil	Hypoglycaemia weight gain	Can use at any level of renal function. But use cautiously in CKD as there is increased risk of accumulation and hypoglycaemia. Prefer gliclazide (predominantly hepatic excretion). Start gliclazide 40mg daily if eGFR<30, then adjust to response.
	Gliclazide	Glyade Nidem
	Gliclazide MR	Glyade MR Diamicron MR
	Glimepiride	Dimirel Amaryl
	Glipizide	Minidiab, Melizide
DPP4 – Dipeptidyl peptidase-4 inhibitors inhibit DDP4 which prolongs action of GLP-1 which enhances insulin secretion + inhibits glucagon secretion Mainly improve post-prandial BGLs	Alogliptin	Nesina	0.7–1%	Minimal hypoglycaemic risk	Pancreatitis	Pancreatic disease kidney impairment (dose reduction may be required)
	Linagliptin	Trajenta
	Saxagliptin	Onglyza
	Sitagliptin	Januvia
	Vildagliptin	Galvus
GLP1 – Glucagon-like peptide-1 analogues increase GLP-1 action which enhances insulin secretion + inhibits glucagon secretion Decrease fasting + post prandial BSL	Dulaglutide	Trulicity	0.8–0.9%	Weight loss	Nausea and vomiting RIsk of pancreatitis	contraindicated if CrCl <30 Trulicity – avoid if eGFR<15. Byetta – avoid if eGFR<30 if eGFR 30-50, be cautious when increasing from 5mcg to 10mcg dose. Bydureon – avoid if eGFR<50. contraception is the recommendation with GLP-1 agonists in women should avoid in patients with severe gastrointestinal diseases (gastroparesis and (BD) caution with pancreatic disease, gallbladder disease, family or personal history of thyroid cancer
	Exenatide	Byetta (SR)Bydureon (ER)
	Liraglutide	Victoza
	Semaglutide	Ozempic
SGLT2 inhibitors – Sodium-glucose co-transporter 2 inhibitor slower blood sugar by causing the kidneys to remove sugar from the body through the urine effective in delaying the progression of CKD in people with and without type 2 diabetes	Dapagliflozin	Forxiga	0.5–0.7%	Lowering of blood pressure cardioprotection weight loss	Genitourinary infections Euglycaemic ketoacidosis Avoid use with loop diuretics.	contraindicated if CrCl <30 approved for – Type 2 DM – HFrEF : Dapagliflozin, Empagliflozin – CKD (stage 2, 3 or 4 and urine ACR≥ 30 mg/g) : Dapagliflozin
	Empagliflozin	Jardiance
	Ertugliflozin	Steglatro
Insulin	Superior to other diabetes drugs			Nil	Hypoglycaemia weight gain	Inability to safely administer insulin or monitor glucose
Alpha glucosidase inhibitor	Acarbose	Glybosay	0.8%	Nil	weight neutral Gastrointestinal symptoms – bloating – flatulence	contraindicated if – CrCl <25 mL/min – Gastrointestinal disease note: glucose (not sucrose) must be administered to treat hypoglycaemia
Thiazolidinediones	Pioglitazone	Acpio, Actaze, Actos, Vexazone	0.7–0.8%	Nil	Fluid retention Increased risk of non-axial fractures in women, Weight gain Worsening of heart failure Macular oedema Cardiac ischaemia Bladder cancer	Patient must have a contraindication or intolerance to metformin- sulfonylurea combination

Diabetes – Medications