تعليق
3.3.1 TB treatment regimens
The same TB treatment regimen should be prescribed for people living with diabetes as for people without diabetes, including the recent shorter regimens for drug-susceptible and drug-resistant TB. Details of TB treatment regimens can be found in the respective consolidated guidelines on the treatment of drug-susceptible and drug-resistant TB and in subsequent updates on the WHO TB Knowledge Sharing Platform (29,30).
People living with diabetes may present with a number of risk factors for clinical complications, more severe adverse events and toxicity such as hepatotoxicity and drug–drug interactions, which may result in poorer TB treatment outcomes (109). Vigilance for possible side-effects and drug–drug interactions and support for adherence to treatment are therefore critical during TB treatment. In people living with diabetes, glycaemic control optimizes the chance of cure and is associated with a lower risk of recurrence (101). Controlling glucose levels in people with diabetes and TB requires close monitoring and adjustments to glycaemic management, potentially involving insulin. Access to qualified personnel with experience in initiating and monitoring insulin and monitoring to ensure prompt identification and management of side-effects might therefore be necessary. Counselling should also be provided to encourage identification and early reporting of symptoms of side-effects (e.g. peripheral neuropathy), as some side-effects may necessitate a change in regimen.
Side-effects in people living with diabetes on TB treatment
- Eye examination is recommended before and during TB treatment.
- Ethambutol may increase ocular neuropathy, and baseline optic nerve, retinopathy or maculopathy may worsen after linezolid use (101,116–118).
- People living with diabetes are at increased risk of optic neuritis and peripheral neuropathy, which may be further exacerbated by exposure to linezolid, isoniazid or cycloserine (101).
- Pyridoxine prophylaxis can help to prevent most cases of neuropathy, with the exception of linezolid (101).
- In individuals with diabetes and impaired kidney function, careful consideration of drug dosages and monitoring of renal function are essential to ensure safe, effective treatment of TB and to reduce the risk of drug-related complications. Caution should be exercised when using aminoglycosides (e.g. streptomycin, amikacin), although these are now used only in individualized regimens to treat people with multidrug- or rifampicin-resistant tuberculosis (MDR/RR-TB) when other regimens cannot be used (101).
- Concomitant use of metformin at high doses and of linezolid may increase the risk of lactic acidosis (116).
Drug-drug interactions during co-management of TB and diabetes
- Glucose-lowering medication might influence the pharmacology of some anti-TB drugs (e.g. rifampicin), which might increase the risk of acquired drug-resistance (101).
- Rifampicin is a potent hepatic enzyme inducer, increasing the hepatic metabolism of sulfonylurea derivatives and therefore lowering their plasma levels.
- Rifampicin is not known to affect the exposure of glucagon-like peptide-1 receptor agonists, and it has only a slight effect on dipeptidyl peptidase-4 inhibitors (12).
- The glucose-lowering effect of metformin may be increased by rifampicin (119).
- Case reports and results from animal studies indicate that linezolid may increase the hypoglycaemic effects of glucose-lowering medication (121–123).
- Studies indicate that certain fluoroquinolones, such as gatifloxacin and levofloxacin, influence glucose metabolism and cause abnormal glucose regulation with hypoglycaemic effects shortly after the beginning of quinolone therapy and hyperglycaemic effects later in the treatment course (124–126).
- The use of steroids can significantly impact glycaemic control in people with comorbid diabetes. Therefore, dose adjustment of glucose-lowering medication should be considered when managing TB-meningitis and diabetes (127).
- In people receiving treatment for TB, diabetes and HIV, metformin does not interact with protease inhibitors, but its exposure increases with dolutegravir. Adjustment of the dose of metformin should be considered when starting or stopping dolutegravir to maintain glycaemic control. High doses of metformin should be avoided, and close monitoring of people with moderate renal impairment is recommended (128).
3.3.2 Integrated service delivery and ambulatory care
National TB Programmes and NCD programmes should plan to deliver integrated care for TB and diabetes, preferably at the same time and location, with due consideration to preventing TB transmission. To ensure infection control, management of the two conditions is ideally based at the TB clinic, at least until the early stages of TB treatment are completed. This may require capacity-building and mentoring of the health-care workers providing TB care and close collaboration between the TB and diabetes services. Where the infrastructure allows, provider-to-provider telemedicine may be considered for virtual integration (129).
Early ambulatory care is recommended, including for the management of DR-TB with the latest recommended DR-TB regimens, because it complements the people-centred approach to the management of TB (29). Every attempt should be made to put people with DR-TB on all-oral regimens unless there are clinical indications for hospitalization, such as in cases of hyperglycaemic emergency, severe TB lung disease with signs of respiratory distress or failure, sepsis or serious adverse reactions to medication (130).
3.3.3 Treatment support and social protection
The social determinants of health are not only driving the diabetes and TB epidemics but also make it difficult for affected people to adhere to treatment, particularly if they have another comorbidity such as a mental health condition. People with TB and diabetes often experience stigmatization and discrimination in many areas of life, including work, social activities and family life. Social, economic, cultural and legal issues may pose additional barriers in accessing health care and the ability to follow medical advice consistently. Consequently, it is important that health-care services are aware of all the barriers faced by people affected by TB and diabetes and that they provide appropriate, comprehensive social support and social protection to facilitate adherence and reduce economic hardship. Interventions to ensure treatment adherence can include material support (e.g. food, financial enablers, transport fees), psychological support, tracers such as home visits or digital health communication (e.g. SMS, telephone) and medicine monitoring (30,31). Treatment support, preferably in the community or at home with options for video-supported treatment, are also recommended by WHO. Interventions should be selected after an assessment of the individual’s barriers to access, needs and preferences, as well as their resources. Education and counselling on TB and its treatment should be provided to all people with TB. For people with diabetes and TB, specific education on managing their diabetes while taking TB treatment should also be provided.
