Diabetes and hypertension remain the most common public health problems in the world and are the major risk factors for cardiovascular diseases that are the leading cause of death.¹ Globally, both diseases affected nearly 2 billion people, with 1.4 billion hypertensive subjects and 425 million diabetic subjects, and accounted directly for 7.5 million and 1.6 million deaths respectively in 2017 (World Health Organization). The pharmacological treatment using antihypertensive and antidiabetics is core to any medical procedure for resolving these chronic diseases in any population, especially in developing countries where the availability of the pharmaceutical products remains a real challenge for governments in terms of both the technological innovation (generics penetration) and the economic burden.² Daily use of these medications, and for long terms, is a complicated process affected by the psychological adjustment of subjects, their socioeconomic status and the mixture of compounds for treating the chronic conditions, regarding their effectiveness, their adverse reactions, their cost and their availability. To achieve positive therapeutic goals represented by positive clinical outcomes, and therefore prevent macrovascular and microvascular complications, subjects have to adhere to long-term guidelines and strategies for diets and pharmacological treatment following prescribed daily doses.^3,4 Generally, for diabetes and hypertension, there are two major indications for changing the medication: a therapeutic failure and/or the appearance of serious adverse reactions or discomfort. The antidiabetics have varying effectiveness and with several side effects,⁵ whilst the hypertension treatment has been revolutionised by the introduction of many new classes; particularly, the calcium channel blockers (CCB), the angiotensin converting enzyme inhibitors (ACEI), the angiotensin receptor blockers also called (also called T-blockers), the diuretics and other drugs that are cost-effective safe. In Morocco, as in many other African countries, there is a paucity of use of antihypertensives and antidiabetics amongst the general population. This study aimed to contribute to developing a picture of the pharmacoepidemiological profile of antihypertensives and antidiabetics in Morocco for academic purposes.

Our sample comprises 244 subjects with a mean age of 60.64 (s.d. ± 12.90) years which form a population of diabetic subjects (56.96%; n = 139) and hypertensive subjects (43.03%; n = 105) and were predominantly women (58.15%; n = 142) (p < 0.03) selected randomly from various geographic locations, rural areas (59.01%) and urban areas (40.98%) in one prefecture. Table 1 summarises the main characteristics of the population.

This is the first observational pharmacoepidemiological investigation of antidiabetics and antihypertensives utilisation in one prefecture in Morocco.

In Morocco, since 2011, the generalisation of the basic healthcare insurance, especially amongst needy populations, has been improving the healthcare access, chiefly the pharmacological treatment.¹⁰ Affected by the expansion of the national pharmaceutical market, the consumption of these drugs has increased drastically in the last decades, encouraged by the generic penetration and advancement of the therapeutic innovations in Morocco.

In terms of antidiabetics, our findings pointed out the widespread use of the biguanides, both in monotherapy and in association with various antidiabetic agents, and defined the same epidemiological pattern in other developing African countries.^11,12,13 The national pharmaceutical market of antidiabetics progressed from ranging over six specialties (1991) to 16 specialties (2005) translating the huge demands for these agents, evolving from 1.9 to 14 DDD/1000 inhabitants/day (DDD = defined daily dose) from 1997 to 2014.¹⁴ Analyses show that the national consumption of sulfonylureas and metformin have increased by four and 10 times respectively from 1997 to 2004. Our results show that 21.37% of diabetic patients experienced discomfort with their pharmacological treatment. A prospective study¹⁵ of oral antidiabetics amongst Moroccan diabetic patients indicated that 50% of those patients experienced adverse reactions, mostly related to metformin (95%) and sometimes did require the interruption of treatment, whilst sulfonylureas were mainly linked to hypoglycaemia as their side effect (0.5%).

Most of the antidiabetics described in our survey are available in public health facilities as part of the national health policy for managing chronic diseases (2012).¹⁰ The class of biguanides is generally well-tolerated compared to insulin, is inexpensive, acts by decreasing the insulin resistance, inhibits hepatic gluconeogenesis and opposes the action of glucagon. Their preventive actions on the cardiovascular system were confirmed in 53 observational and experimental studies¹⁶ (Hazard ration HR 0.78, 95%, CI 0.73–0.83, p < 0.00001) as compared to the insulin group. Their main adverse reactions include nausea, abdominal discomfort and some diarrhoea.¹⁷ Generally, metformin has to be taken with meals in an increasing dose as tolerated. A retrospective cohort study¹⁶ conducted in England and Wales has linked insulin with an increased risk of composite non-fatal acute myocardial infraction, which causes death and non-fatal stroke (HR 2.6, 95%, CI 1.9–3.4). The association of biguanides with insulin¹⁶ was linked to gastroduodenal discomfort, weight loss and hypoglycaemia. The class of sulfonylureas¹⁷ acts as insulin secretagogues, and as β-cell pancreatic dysfunction progresses, they become less effective. They are inexpensive, but their main adverse reaction includes symptomatic episodes of hypoglycaemia.

In Morocco, the use of antihypertensive drugs increased from 0.08 to 10.65 DDD/1000 inhabitants/day between 1991 and 2010 with a dominance of CCB drugs (82.09%) followed by ACEI drugs (48.29%).¹⁸

Our findings reveal that drugs acting on the renin–angiotensin aldosterone system (RAAS) are widely used in monotherapy (37.89%) represented by two major pharmacological classes: ACEI and T-blockers. Generally, they are considered as the first line and are quite effective in the management of hypertension.¹⁹ The most important adverse reaction²⁰ in this group is represented by dry cough because of increase in bradykinin concentration which may constitute an indication to switch from ACEI to T-blockers. Other side effects include angioedema, hyperkalaemia and diarrhoea.²¹ When combined with β-blockers, they have additive cardio-protective actions with less antihypertensive action.²² The second major pharmacological class was represented by CCB represented with its two subgroups: the Phenylalkylamine (verapamil) and dihydropyridine (amlodipine).²³ Their pharmacological antihypertensive action resulting in vasodilatation is considered more effective than the ACEI and β-blockers, especially in the African population.²⁴ Their adverse reactions are dose dependent, because of their vasodilatation actions, and essentially include gastrointestinal problems (constipation associated with Verapamil in 13%), headache, dizziness, light-headedness, flushing, hypotension and peripheral oedema (10% – 20% of all patients) more commonly found in women and probably because of an increased capillary pressure and for which the association with diuretics may not reveal this oedema, whilst the association with ACEI or T-blockers may reduce or prevent it.^23,25 The results of 22 clinical trials²⁴ show lower incidence of diabetes compared to diuretics and β-blockers but greater than ACEI and T-blockers. Their association with diuretics is acceptable considering that they excrete sodium preventing the volume depletion that occurs with diuretics and their help in reduction of cardiovascular risks.²⁶ The third antihypertensive class represented by the diuretics contains three major groups of compounds depending on their pharmacological actions: the thiazides (hydrochlorothiazide and indapamide), the loop diuretics (furosemide) and the potassium spearing diuretics (spironolactone).²⁷ The main adverse reactions of diuretics include headaches, dizziness, increased blood glucose, gout, diarrhoea, kidney failure and irregular heartbeat. They reduce the intravascular volume and activate the Renin Angiotensin Aldosterone system (RAAS) leading to vasoconstriction and the retention of sodium and water.²⁸ Therefore, the association with an ACEI or T-blockers attenuates this irregularity and ameliorates the hypokalaemia with an increasing risk of hyperkalaemia.²⁹

The β-blockers are used as a second line of hypertension management, especially amongst patients who survived an acute myocardial infraction, heart failure and atrial fibrillation by reducing the heart’s rhythm. When compared to ACEI, T-blockers and CCB, the β-blockers have a reduced action on hypertension.^30,31 Their adverse reactions, which can be explained by understanding their molecular mechanism and competitive antagonist action on c-adrenoceptors, include interference with heart rate, hypotension, hypoglycaemia, abdominal pain, nausea, vomiting, constipation, dizziness, depression and many others.³²

In this survey, 6.9% of all participants have associated chronic conditions, such as asthma, rheumatism, psychological disorder and epilepsy which increase the complexity therapeutic not only for the subjects but also for health professionals as it increases the risk of drug–drug interactions. Our findings show an adjusted prevalence of polypharmacy³³ in 1.22% observed diabetic subjects. We consider two major factors that determine the success of combination therapies:

Our sample was representative of registered patients in the prefecture (nearly 10%); extrapolation to the general population should consider the ethnic diversity (Arabs and Amazigh) and the socioeconomic variations that characterise the Moroccan population and which may affect the lifestyles.

Further investigations are required to define new strategies of side effects of medication in long-term use.

Managing diabetes and hypertension still pose a lot of public health challenges and requires more focus and interest, especially amongst the illiterate population in remote areas. The management measure should include the introduction of new innovative measures, systems of follow-up and adverse reactions management, at the individual, regional and national levels.