Table 3 Conjoint display utility and non-utility measures of outcomes importance

HbA1c (glycaemic control)

Glycaemic control is an expected treatment outcome, usually preferred over avoiding hypoglycaemic events (104). Achieving glycaemic control obtained a high overall willingness to pay despite some variability within and across studies (28 to $205 US/month across) reported in five studies conducted in Europe, USA and Australia, included in a systematic review (104).

Utilities showed no differences when comparing poor control 0.85 (95% CI 0.80 to 0.90) vs. excellent control 0.87 (95% CI 0.82 to 0.92) (EQ-5D) in a study conducted in Japan [105, 106].

Poor glycaemic control is frequently associated with negative behaviours, impatience, and fatalistic beliefs or being just aware of their HbA1c values but not feeling confident and motivated to improve their diabetes [26, 29, 60].

Patient reactions to self-monitoring blood glucose (SMBG) results vary and are often subjective. While some patients have few problems, others see SMBG as a burden that has a significant impact on their lives, causes anxiety, and leads to numerous internal and external psychological conflicts [56, 63, 86].

Expansion /discordance

Overall, both sources of evidence complement each other. Quantitative findings describe the desirability of achieving glycaemic control, while qualitative findings describe the experience of not achieving glycaemic control and the burden associated with self-monitoring.

However, contradictory findings were described for poor control. Unexpected findings in one study conducted in Japan, showed similar impact on health for poor and excellent control.

Weight change

The impact of extreme obesity on health is twice as important as being overweight. Extreme obesity has a mean utility value of 0.400 (95% CI 0.363 to 0.437), while obesity and overweight have 0.8 (EQ-5D) [105, 107, 108]

Fears of weight gain or the inability to lose it was a common worry that mediated insulin adherence [52, 56, 90). Weight loss was an expected benefit of adherence to treatment for some patients (52).

Expansion

Weight changes concerns in utility measures is described as the impact of the severity of obesity, whereas in the qualitative findings it is linked to the effect of treatment.

Long-term complications

The most important outcomes expressed by utility values were long-term complications, including diabetic peripheral neuropathic pain (0.468, 95% CI 0.372 to 0.565) [105, 107, 109), blindness (0.529, 95% CI 0.393 to 0.665) [105, 110], and amputation (0.537, 95% CI 0.453 to 0.621) [105, 107, 111].

Cardiovascular risk

When patients were asked about the importance of the effects of therapy on the risk of cardiovascular disease, some patients assigned a high, but not primary, importance, to not experiencing a heart attack episode within the next year. Others, consider the reduction of cardiovascular risk, in general, to be of minor importance (104).

Patients’ estimation of the risk of long-term complications is variable.

Patients usually have limited or erroneous comprehension of diabetic foot ulceration and amputation [53].

Cardiovascular risk

Patients tend to underestimate cardiovascular risk [65].

Expansion/Confirmation

Quantitative utility-based measures provided more detailed and extensive findings regarding long-term complications than qualitative findings, which were scarce and generic.

For cardiovascular risk, findings tend to be consistent, highlighting low-risk perception.

SM burden

Diet and exercise reported the highest utility values (0.765, 95% CI: 0.684 to 0.846, I2: 93.9%).

Results were similar for intensive blood glucose control and usual care (0.737, 95% CI: 0.640 to 0.833; and 0.737, 95% CI 0.677 to 0.798, respectively).

Adherence to SM requires training and time to integrate into everyday life and adjust to contextual factors.

Accessing healthcare can be difficult in some contexts. Attendance to clinical appointments varies according to previous experiences. Most patients experience constraints on quality of life and physical and psychological barriers that make it challenging to adhere to SM. SMI with adequate support enhances patients’ self-efficacy.

Discordance

Indirectly, SM burden can be measured by how patients valued diet and exercise, intensive SM and usual care.

No difference was showed between intensive blood glucose control and usual care. A possible explanation is that these values were obtained in clinical trials.

In contrast, qualitative findings describe the extra burden patients experience especially when start integrating SM in everyday life.

Hypoglycaemia

Hypoglycaemia values varied according to severity. The worst values were for major hypoglycaemia and events with very severe symptoms or presented at night. Mean utility values ranged from 0.540 (95% CI: 0.500 to 0.580) for very severe hypoglycaemic symptoms to 0.800 (95% CI: 0.760 to 0.840) for hypoglycaemic non-severe symptoms. Major hypoglycaemia impacts three times more than minor hypoglycaemia (0.159 (SD 0.11) and − 0.045 (SD 0.028), respectively). In Discrete choice experiment (DCE) studies, willingness to pay to avoid hypoglycaemia varied from 45 US$ to 104 US$/month, with higher values for night-time events (72 US$ to 94 US$) [90, 104, 112] and for one event less of major hypoglycaemic per year (80 US$ to 104 US$) [112].

Many patients do not experience warning signs of hypoglycaemia, and it is not easy for them to understand their new bodily reactions. Hypoglycaemia is a significant concern for patients, impacting their emotional state, daily functioning and engagement with insulin. Insulin-related nocturnal hypoglycaemia is associated with a disrupting effect on diabetes SM, including sleep quality and next-day functioning, work performance and driving, negative financial consequences and quality of life or personal well-being. Hypoglycaemia causes fear and is associated with reduced adherence to treatment and high blood glucose levels.

Hypoglycaemia represents a challenge for patients and their families. Family members may need to take control in acute situations, for which they need information and resources [43, 46, 52, 54, 56,57,58,59, 78, 84,85,86, 88].

Confirmation

Both sources of evidence describe how burdensome hypoglycaemia is, especially nocturnal hypoglycaemia. The impact of severity is better described in quantitative data,

whereas qualitative findings confirm the significant concern that hypoglycaemia represents, the implications for quality of life, and adherence to treatment and SM.

Quality of life

and Psychological distress

Patients with T2DM usually feel a myriad of emotions related to the diabetes diagnosis, complications and SM, often overwhelmingly negative. They perceive a loss of confidence, the disruption of usual roles, and a sense of independence. Most patients feel that the disease is “taking over their lives”, threatening how they identify themselves or their “sense of identity”. Diabetes stigma, or patients’ expressions of embarrassment and moral failure associated with T2DM, can be related to the diagnosis, complications and medication use. Stigma may prevent patients from disclosing their diagnosis, impairing their ability to self-manage and negatively influencing medicine-taking behaviour, especially insulin treatment.

When accepting the disease, patients can feel supported by others. Family is an essential motivator to adhere to diabetes SM. However, for some patients, family support is perceived as interference. Talking to similar others and sharing experiences is an essential source of emotional support [41, 43,44,45,46,47,48,49, 51, 53,54,55,56,57,58, 70, 71, 73, 78, 80, 84,85,86, 88, 89].

No data was found in quantitative utility-based measures.

Lipid control

Some patients do not perceive the benefit of taking medicines for lipid control. The absence of symptoms and the lack of awareness of the increased risk for cardiovascular disease are potential explanations for this attitude [65, 71, 104].

No data was found in quantitative utility-based measures.