Biology • Year 12 • Module 8 • Lesson 14
Treating One Non-infectious Disease: Type 2 Diabetes
Apply the Type 2 diabetes mechanism to trial data, an HbA1c trend, a treatment-choice case study and a comparison task, practising the reasoning required for Band 4–5 HSC responses.
1. Interpret trial data, weight management and remission
The table summarises twelve-month results reported by the DiRECT trial of structured dietary weight management in Type 2 diabetes, alongside a separate prevention trial in people with prediabetes. Use the data to answer the questions. 8 marks
| Study and group | Outcome measured | Result |
|---|---|---|
| DiRECT, structured dietary weight management | Remission at 12 months | 46% |
| DiRECT, standard care | Remission at 12 months | 4% |
| Prevention trial, intensive lifestyle change | Reduction in progression from prediabetes to Type 2 diabetes | 58% |
| Prevention trial, metformin | Reduction in progression from prediabetes to Type 2 diabetes | 31% |
1.1 Calculate the difference in remission rate between the two DiRECT groups, and state what that difference suggests about the intervention. 2 marks
1.2 Explain, at the level of the disease mechanism, why substantial weight loss can produce remission. 3 marks
1.3 The prevention trial shows lifestyle change outperforming metformin, yet metformin is still commonly prescribed first once Type 2 diabetes is established. Suggest two reasons why. 3 marks
2. Interpret a graph, HbA1c response to a management plan
The graph shows HbA1c for one patient over 18 months. Lifestyle support began at month 0 and metformin was added at month 6. The individual target agreed with the patient was 7.0%. 8 marks
2.1 Describe the trend in HbA1c across the 18 months, quoting values from the graph. 3 marks
2.2 A student writes: "HbA1c fell, therefore HbA1c treated the diabetes." Identify the error and correct it. 2 marks
2.3 Using the month 12 to month 18 data, justify one decision the clinical team should consider next. 3 marks
3. Cause-and-effect chain, untreated insulin resistance
Complete the chain by writing the missing steps. Each box must state a biological change, not a symptom name alone. 6 marks
Step 1 (given). Muscle, liver and fat cells respond poorly to insulin.
Step 2.
Step 3.
Step 4.
Step 5.
Step 6 (given). Cardiovascular disease, kidney disease, retinal damage and peripheral nerve damage develop over years.
4. Case study, choosing between two effective medicines
A 54-year-old patient has Type 2 diabetes with an HbA1c of 8.6% despite sustained lifestyle change. Two options are discussed. Option 1 is metformin: low cost, subsidised, taken as a tablet, with digestive side effects in some people. Option 2 is a GLP-1 receptor agonist such as semaglutide: it stimulates insulin secretion only when glucose is high, suppresses glucagon, slows gastric emptying and reduces appetite, producing 15 to 17% body weight reduction in trials plus cardiovascular benefit, but it is injected and is far more expensive if not subsidised for that indication.
4.1 Explain how the mechanism of a GLP-1 receptor agonist differs from that of metformin. 3 marks
4.2 "The newer drug produces more weight loss, so it is automatically the better choice." Evaluate this claim. 4 marks
5. Compare lifestyle management and metformin
Complete the comparison table using full sentences. 8 marks
| Feature | Lifestyle management | Metformin |
|---|---|---|
| Point in the mechanism targeted | ||
| One advantage | ||
| One limitation | ||
| Why the two are often combined | ||
Q1, Trial data
1.1 46% − 4% = 42 percentage points [1]. The very large difference between the intervention and standard-care groups suggests that structured dietary weight management, rather than chance or background care, produced the remissions [1].
1.2 Excess visceral fat releases inflammatory adipokines that disrupt insulin receptor signalling [1]. Losing roughly 10 to 15 kg reduces that visceral fat, so signalling normalises and insulin sensitivity returns [1]. Beta cells that were overworking to compensate are relieved and can recover function, so blood glucose returns to the non-diabetic range without medication [1].
1.3 Any two of: sustained behaviour change is difficult and demands time, money, food access and support that not every patient has [1]; metformin is low cost, subsidised, effective and works without requiring that sustained change [1]; the two act through different mechanisms so metformin can be started immediately while lifestyle change is built up, and plans are commonly combined rather than exclusive [1].
Q2, HbA1c graph
2.1 HbA1c falls from about 9.2% at month 0 to about 8.4% at month 6 under lifestyle support alone [1]. After metformin is added at month 6 the fall becomes steeper, reaching about 7.1% at month 12, close to the 7.0% target [1]. Between months 12 and 18 the trend reverses slightly, rising to about 7.4%, so the target is not sustained [1].
2.2 The error is treating a monitoring measure as a treatment [1]. HbA1c did not lower anything; it recorded the average glucose that fell because lifestyle change and metformin acted on insulin sensitivity and hepatic glucose output. HbA1c is the evidence that the treatment worked [1].
2.3 The rise from 7.1% to 7.4% means the person is now above their agreed target and the trend is moving the wrong way [1]. Before escalating, the team should review adherence, access, diet, activity, intercurrent illness and side effects, since a plan that is not being followed is not the same as a plan that has failed [1]. If the plan is being followed and beta-cell function is still declining, escalation by adding another medicine or insulin should be considered [1]. Accept any well-justified decision that uses the trend as evidence.
Q3, Cause-and-effect chain
Step 2. Glucose uptake from the blood falls, so blood glucose stays higher than normal after meals [1].
Step 3. Pancreatic beta cells detect the raised glucose and secrete more insulin to compensate, so glucose is held near normal for a period [1].
Step 4. Sustained over-secretion cannot be maintained, and beta-cell function progressively declines (beta-cell exhaustion) [1].
Step 5. Insulin output can no longer match demand, so blood glucose remains persistently elevated (chronic hyperglycaemia) [1].
Award up to 2 further marks for correctly linking persistent hyperglycaemia to progressive damage of blood vessels and nerves as the mechanism by which Step 6 follows.
Q4, Case study
4.1 Metformin acts mainly on the liver and peripheral tissues: it reduces hepatic glucose output and improves insulin sensitivity, and it does not stimulate insulin secretion [1]. A GLP-1 receptor agonist mimics the gut hormone glucagon-like peptide-1, stimulating insulin secretion in a glucose-dependent way, so only when glucose is high, and suppressing glucagon [1]. It also slows gastric emptying and reduces appetite, which is why it produces substantial weight loss, an effect metformin does not match [1].
4.2 The claim is partly supported: the 15 to 17% weight reduction is the largest non-surgical effect yet reported and weight loss addresses the insulin-resistance mechanism directly, with additional cardiovascular benefit [1]. However, effectiveness is not the only criterion. Trial efficacy commonly shrinks to lower real-world effectiveness because adherence, cost, health literacy and access intervene [1]. A far more expensive injected medicine that is not subsidised for this patient may be less useful in practice than a low-cost subsidised tablet the patient can reliably obtain and take [1]. A defensible judgement is therefore that the GLP-1 agonist is more effective on trial evidence but not automatically the better choice; the decision must weigh effectiveness, safety, side effects, cost, access and sustainability for this individual [1].
Q5, Comparison table
Point in the mechanism targeted. Lifestyle management: reduces modifiable drivers of insulin resistance through activity, nutrition and, where appropriate, weight change, and exercise also drives insulin-independent glucose uptake via GLUT4 [1]. Metformin: reduces glucose released by the liver and improves how tissues respond to insulin [1].
One advantage. Lifestyle: broad cardiovascular and metabolic benefits, no drug side effects, and can produce remission [1]. Metformin: effective, low cost, widely available and does not depend on sustained behaviour change [1].
One limitation. Lifestyle: difficult to access and sustain, and shaped by time, cost and social context [1]. Metformin: digestive side effects in some people, contraindications in some patients, and it does not cure the disease or remove every underlying risk [1].
Why combined. The two act through different but complementary mechanisms, so combining them can control glucose better than either alone, and monitoring evidence allows each part to be adjusted over time [2].