Type 2 diabetes mellitus

E11.0-9/E12.0-9/E13.0-9/E14.0-9

Management includes:

  • Treatment of hyperglycaemia.
  • Treatment of hypertension and dyslipidaemia after risk-assessment. See Hypertension.
  • Prevention and treatment of microvascular complications.
  • Prevention and treatment of macrovascular complications.

MEDICINE TREATMENT

Oral blood glucose lowering drugs

Metformin is the preferred initial medicine and is added to the combination of dietary modifications and physical activity/exercise. If metformin, in maximal dose, with diet and exercise fails to lower HbA1c to target, a second agent should be added. This second agent may be either a sulphonylurea, or basal insulin. The specific indication is dependent on individual circumstances.

If a combination of two agents fails to lower HbA1c to target, a third agent is added. The preferential sequence of agents to use is metformin, followed by the addition of sulphonylurea, followed by the addition of basal insulin.

If the combination of two oral agents and basal insulin fails to lower HbA1c to target, or if other reasons to adjust therapy exist (such as nocturnal hypoglycaemia), then intensified insulin therapy in consultation with a specialist is required (either twice daily pre-mix, or basal-bolus therapy) and sulphonylureas are discontinued.

Note: Secondary failure of oral agents occurs in about 5–10% of patients annually.

Metformin

  • Metformin, oral, 500 mg twice daily with meals.
    • Adjust dose based on fasting blood glucose levels and/or HbA1c to a maximum dose of 850 mg 8 hourly.
    • Monitor renal function.
    • Dose-adjust in renal impairment as follows:

LoEI [12]

eGFR Metformin dose
eGFR >60 mL/min: Normal daily dose (see above).
eGFR 45–60 mL/min: Standard dose, measure eGFR 3–6 monthly.
eGFR 30–45 mL/min: Maximum dose 1 g per day; measure eGFR 3–6 monthly.
eGFR <30 mL/min: Stop metformin.
  • Contra-indicated in:
    • renal impairment i.e. eGFR <30 mL/minute,
    • uncontrolled congestive cardiac failure,
    • severe liver disease,
    • patients with significant respiratory compromise, or
    • peri-operative cases.

LoEIII [13]

Sulphonylurea derivatives: glimepiride or glibenclamide.

  • Glimepiride, oral, 1 mg daily.
    • Titrate the dose by 1 mg at weekly intervals up to 6 mg daily (according to blood glucose levels).
    • Usual dose: 4 mg daily.
    • Maximum dose: 8 mg daily.

LoEI [14]

OR

  • Glibenclamide, oral, 2.5 mg daily 30 minutes before breakfast.
    • Titrate dose slowly depending on HbA1c and/or fasting blood glucose levels to 15 mg daily.
    • When ≥7.5 mg per day is needed, divide the total daily dose into 2, with the larger dose in the morning.
    • Avoid in the elderly and patients with renal impairment (i.e. eGFR <60 mL/minute).

LoEI [15]

Oral agents should not be used in type 1 diabetes and should be used with caution in liver and renal impairment.

Metformin should be dose adjusted in renal impairment.

Monitor patients on sulphonylurea derivatives and concomitant rifampicin and dose-adjust sulphonylurea as required. When rifampicin is discontinued, monitor for risk of hypoglycaemia and dose adjustment is required, particularly in the elderly.

Monitor serum creatinine and estimated eGFR three monthly in patients with kidney disease.

Insulin therapy in type 2 diabetes

Indications for insulin therapy:

  • Inability to control blood glucose pharmacologically, i.e. combination/substitution insulin therapy.
  • Temporary use for major stress, e.g. surgery, medical illness.
  • Severe kidney or liver disease.
  • Pregnancy.

Note:

  • At initiation of insulin therapy, give appropriate advice on self-blood glucose monitoring (SBGM) and diet.
  • It is advisable to maintain all patients on metformin once therapy with insulin has been initiated.
Insulin type Starting dose Increment Max.daily dose
Add on therapy:
  • Intermediate to long-acting insulin
    		•  10 units, (or 0.3 units/kg/day), in the evening before bedtime, but not after 22h00. If the starting dose is
    not effective increase
    by 2-4 units per dose
    every 3 to 7 days until
    fasting glucose is in the
    target range.     		Refer if recurrent
    hypoglycaemia
    occurs and targets
    for control are
    not met.
    Substitution therapy:
  • Biphasic insulin (30/70 mix)
    		•  Total daily dose: 0.3 units/kg/day divided as follows:
  • 2/3 of total daily dose 30 minutes before breakfast.

  • 1/3 of total daily dose 30 minutes before supper.

    • LoEIII [16]     		4 units weekly.

    First increment is added to dose before breakfast.     		Refer if recurrent
    hypoglycaemia
    occurs and targets
    for control are not
    met.
    Basal bolus insulin therapy Start with 0.4 to 0.6 units/kg and divide this total daily dose into 50% basal and 50% bolus, using equal pre-meal doses Basal insulin is adjusted according to fasting glucose levels and bolus insulin is adjusted according to pre- and post-meal glucose, using the patient’s home glucose record as a guide. Refer if recurrent
    hypoglycaemia
    occurs and targets
    for control are not
    met.

    LoEIII [16]

    Also see insulin protocols Type 1 diabetes mellitus.

    LoEIII [17]

    Note: Insulin requirements decrease in patients with chronic renal impairment. In these situations, blood glucose monitoring must be done regularly (at least daily) in order to reduce the dose appropriately, reducing the risk of hypoglycaemia.

    To reduce cardiovascular risk

    See Dyslipidaemia.

    Renal impairment

    If urine ACR >2.5 mg/mmoL (men) or >3.5 mg/mmoL (women):

    Start treatment with a low dose of ACE-inhibitor and titrate up to the maximum tolerated dose.

    LoEI [18]

    ADD

    • ACE-inhibitor, e.g.:
    • Enalapril, oral.
      • Start with 5 mg 12 hourly and titrate to 20 mg 12 hourly, if tolerated (depending on BP and ACR).

    LoEIII [19]

    See Chronic Kidney Disease.

    If an ACE-inhibitor is not tolerated due to intractable cough, consider an angiotensin II receptor blocker. See Chronic Kidney Disease.