Type 2 diabetes mellitus (T2DM) is amongst the top ten leading causes of death worldwide and continues to burden healthcare systems globally (1). Lower-middle-income countries (LMICs) bear the brunt of this disease, with almost 80% of patients with T2DM belonging to LMICs (2). In Pakistan, a South Asian LMIC with a population of over 220 million, the prevalence of T2DM amongst adults as reported by the International Diabetes Federation (IDF) is more than one in four adults (26.7%) (3). This is the highest national prevalence in the world. As a consequence, Pakistan currently has the third highest number of people living with T2DM in the world, behind only China and India (3), and is predicted to lead the list in the near future (4).

Evidence-based clinical practice guidelines (CPGs) are the cornerstone of the evaluation and management of T2DM. The majority of T2DM CPGs followed internationally have been designed by high-income countries in the West, such as the United States of America (USA) (5, 6), the United Kingdom (UK) (7), and Canada (8, 9). These CPGs have been developed taking into account the healthcare systems of their respective countries, from where, understandably, the majority of the most highly influential T2DM-related research originates (10). Furthermore, LMICs often lack the financial resources and research infrastructure to produce evidence-based CPGs locally and independently (11). This presents a problem, as many factors affecting the management of T2DM differ in LMICs like Pakistan, including epidemiology (3), surveillance systems (12), healthcare costs (13), complication rates (14), sociocultural influences (15), quality of life (16), disease-related awareness (17), health-seeking behavior (17), healthcare infrastructure (18), healthcare access (18), diet (19), and self-care (20). Recognizing this, it is also recommended that even internationally-used best-evidence CPGs need to be modified according to the healthcare context that plans to use them (8). This holds particularly true for LMICs, especially those in South Asia, which suffer from relatively greater burdens of disease.

De novo creation of CPGs is a laborious, resource-intensive process. When not possible due to lack of resources, as is the case in Pakistan and other LMICs, the optimal modification process should be based on a combination of adoption (assimilating existing recommendations as is), adaptation (modification of selected recommendations following critical evaluation), and exclusion (omitting recommendations deemed irrelevant to local context) of existing CPGs (11). Adolopment is a recently introduced word that encompasses three key elements of adoption, adaptation, and development (21).The GRADE (Grading of Recommendations, Assessment, Development and Evaluation)-ADOLOPMENT (11) process uses evidence to decision (ETD) tables to guide this process (22–24). ETD tables provide general and context-specific evidence across standard criteria ( Table 1 ) against which experts judge the overall appropriateness of existing recommendations and proposed modifications. These modifications may be in the form of a change to the specific population, intervention, or control as compared to the original recommendation.

An essential and basic principle of the development of any evidence-based CPGs is a comprehensive, robust, and transparent methodology, as this affects the accuracy, credibility, trustworthiness, and uptake of recommendations (25, 26). In addition to the general challenges faced by LMICs in developing and disseminating CPGs, the Pakistani health system has struggled in achieving mainstream uptake of CPGs by physicians in the country. Initiatives to create CPGs for the management of T2DM have been undertaken in Pakistan, such as the Pakistan Endocrine Society (PES) guidelines (2020) (27) and the PROMPT (Pakistan’s Recommendations for Optimal Management of diabetes from Primary to Tertiary care level) CPGs (created in 1999; revised in 2017) (28). However, these have not achieved nationwide penetrance into routine clinical practice (28). Though both refer to numerous international CPGs, they do not explicitly explain the methodologies used to assimilate and synthesize recommendations, with the PES guidelines simply stating that their CPGs were “based on available local, regional and international scientific evidence including special considerations to affordability and availability of medicines in Pakistan and consensus statements by Guidelines committee of PES”. This ambiguity in the processes followed in the development of the CPGs may underlie their underwhelming uptake locally. Thus, the use of adolopment to generate CPGs for the management of T2DM in Pakistan has the potential to address local challenges on multiple fronts. In addition to being context sensitive and resource efficient, adolopment incorporates granular detail and documentation that is informative and can be understood, appraised, and ultimately accepted by healthcare providers across the country.

The management of T2DM has increasingly become a responsibility of primary care/general practitioners (GPs) as disease burden in Pakistan increases, and the evidence suggests that patient outcomes may remain at par with specialist care if there is an emphasis on regular follow-ups and the use of quality management guidelines (29). Consequently, there is immense need for local T2DM CPGs to be developed for use by GPs, by following a transparent, standardized process that makes use of existing available best-evidence CPGs with appropriate context-specific modifications. Such CPGs would bring the healthcare system of Pakistan a step closer to achieving optimal health outcomes in T2DM and would have greater credibility by virtue of their transparent development processes. Thus, we aimed to employ the GRADE-ADOLOPMENT process to develop local evidence-based CPGs for the management of adult DM by GPs in Pakistan. Furthermore, our goal was to transparently present our methodology for benefits that are twofold. Firstly, researchers in high-income settings can observe how their work is adapted for use in regions like Pakistan. Secondly, guideline creators in LMICs, particularly in South Asia, can build upon and adapt our work to provide CPGs for use in their own local contexts.

In this paper we describe the GRADE-ADOLOPMENT process employed for the creation of evidence-based adult DM CPGs for Pakistan. We aimed to produce a CPG, using a rigorous and transparent methodology, suited to implementation in the local healthcare context of Pakistan. With the Standards of Medical Care in Diabetes – 2021 (Abridged for Primary Care Providers) (5) used as the source guideline, the adolopment process resulted in 1 adapted recommendation and 18 excluded recommendations. Minor changes or associated comments were attached to five of the remaining recommendations which were otherwise adopted directly.

The adoloped adult DM CPG for Pakistan recommends initiation of screening for DM/prediabetes in all Pakistanis after the age of 30 years, as opposed to the original recommendation of 45 years of age in the source CPG. Interestingly, the subsequent edition of our source guideline, the Standards of Medical Care in Diabetes – 2022 Abridged for Primary Care Providers, also updated its recommendation for screening, lowering the age to 35 years (33). This change was based off the US Preventive Services Task Force (USPSTF) statement in August 2021 regarding the need for and benefits of earlier screening (34). Our newly adapted recommendation also adds to current PES and PROMPT CPGs, which do not provide any explicit recommendations for the age after which individuals should be screened (27, 28). This is a significant omission for several reasons. The prevalence of T2DM in Pakistan is an overwhelming 26.7%, as reported by the IDF (3). Of these patients with T2DM, over 25% are aged <40 years and 50% are between 40 and 59 years of age (35). Thus, a large proportion of patients in Pakistan developed T2DM, or were at risk of developing T2DM, before the age of 45 years. Therefore, the age at which screening ought to be initiated must be stated and correspondingly lowered to enable the early detection and management of T2DM. In India, a LMIC with similar T2DM prevalence, the current guidelines in use by the National Program for Prevention and Control of Cancer, Diabetes, Cardiovascular Disease and Stroke (NPCDCS) states that the screening process for T2DM should be initiated at the age of 30 years (36).

It is well established that individuals originating from South Asian countries like India, Bangladesh, Sri Lanka, and Pakistan are at a particularly high risk of suffering from T2DM and its multitude of complications. This increased risk of disease and associated morbidity is attributed to factors such as poor maternal nutrition and impaired intrauterine growth, high rates of childhood obesity, and ever-increasing proportions of fats and sugars in typical diets in these regions (37). Early detection and appropriate management of T2DM is thus crucial for preventing avoidable morbidity and mortality, particularly its debilitating late-stage multi-organ complications in the Pakistani and other South Asian populations. Without region-appropriate age cut-offs for screening of T2DM based on epidemiological evidence, countermeasures largely take the form of tertiary prevention, whereby patients with T2DM present due to the onset of systemic complications (38). These include diabetic eye disease, neuropathy, peripheral arterial disease (with manifestations including diabetic foot ulcers and delayed wound healing) (39). By this point the disease may have taken a severe and frequently irreversible toll on their health, functionality, and quality of life. By initiating screening after the younger age of 30 years in Pakistan, patients and their physicians may act earlier and more effectively to slow disease progression and avoid serious complications (40). Apart from benefiting from earlier pharmacologic intervention, younger patients are also more likely in general to be able to implement lifestyle modifications and are more proactive regarding their healthcare (40–42). Earlier screening highlights the opportunity to intervene early on and reduce complications. It also represents a greater opportunity to promote physical activity to patients in Pakistan, emphasizing the essential role of aerobic exercise and resistance training in enhancing insulin sensitivity to maintain and restore glycemic control (1).

Of particular concern are the economic costs borne by individuals and the community because of the effects of T2DM associated morbidity on their careers and productivity (43). T2DM debilitates individuals and induces complications that hinder their ability to work jobs and earn a living, with a particularly aggressive disease phenotype in cases with earlier onset (44). Furthermore, younger patients with T2DM have severe stress and impaired emotional well-being, with greater rates of depression and fear (45). The possible consequences of such psychological burdens on patients’ social lives, including activities like parenting, as well as mental health and quality of life (46), are concerning. Thus, with its alarmingly high prevalence in Pakistanis of a working age, T2DM represents a burden on all spheres of these patients’ lives and likely causes economic costs to individual patients, their families and communities, and the country. The monetary losses borne by patients quickly add up when considering the loss of time, health, and productivity, as well as the expenditure in procuring drugs, devices for CGM (continuous glucose monitoring) such as glucometers (47), or simply seeing a physician. In this vein, implementation of screening after the age of 30 has the potential to be cost saving to patients (48, 49), a crucial benefit in the LMIC setting of Pakistan, where most healthcare expenditure is out-of-pocket (50–52). This lack of health insurance (or other risk pooling systems of healthcare financing) is also thus a reason for excluding one of the recommendations from the source guideline ( Figure 2 ). Physicians must consider the high cost of care when planning management with patients in LMICs, noting particularly the fact that urgent and expensive interventions for late-stage complications confer a greater financial risk (53, 54). Furthermore, the adopted recommendations involving CGM were coupled with the acknowledgement that obtaining glucometers or similar technology may not be economically feasible for patients in Pakistan. Affordability of care is indeed a crucial point of consideration in T2DM care in an LMIC setting, as burdensome medical expenses can negatively impact patients’ lives or interfere with their adherence to therapy.

A crucial aspect of developing evidence-based CPGs is to use a rigorous and transparent methodology. A systematic and transparent approach is more likely to produce effective and feasible guidelines with greater credibility and adoption by local physicians (25, 26). The absence of documented and transparent methods, beyond cursory details, may explain the low utilization of existing guidelines for the management of DM in Pakistan (28). It may also explain why neither of the currently available sets of CPGs address the matter of screening, despite the evidence pointing to it requiring alteration to a younger recommended age in Pakistan. The GRADE-ADOLOPMENT method overcomes this flaw by grounding its output in a high-quality source CPG created by highly qualified experts who spared no resource in systematically analyzing all the available literature to form recommendations.

The GRADE-ADOLOPMENT method has the added advantage of identifying key avenues for future research. Focusing areas of study can generate evidence while still working within resource constraints, without incurring costs or dedicating resources or personnel to generating evidence that is unlikely to influence policy or clinical decision making. The level of evidence supporting our adapted guideline is a GRADE B as per the GRADEPro methods used (55). Future research should explore the effectiveness of screening earlier to provide higher quality of evidence to support or refute the new recommendation. Additionally, the research and development of new drugs and tools for DM must be more mindful of the target population of diabetics, which primarily resides in LMICs as stated earlier. Though of great value in wealthier countries, tools such as CGM devices can only be as impactful as they are accessible. Their relative costliness highlights the need for affordable technologies and treatment modalities that can achieve widespread adoption in LMICs to reach most diabetic patients, who live in conditions of financial constraints. To sum up, a systematic and disclosed methodology produces credible guidelines more likely to achieve high penetrance locally, while also guiding future research and facilitating a continuous process of improvement over time as the availability of evidence improves and the disease profile of T2DM in Pakistan evolves.

There are limitations to our adolopment process and the newly adoloped Pakistani T2DM CPG that we wish to acknowledge. Fundamental to the GRADE-ADOLOPMENT process, the revision made to age of screening initiation was based on expert consensus informed by suboptimal level of evidence. Moreover, we did not include other important stakeholders, such as patients, allied health professionals, general practitioners, nurses, experts external to AKU, other healthcare centers, external organizations or societies concerned with DM management, and provincial and federal governments. The decision to limit widespread stakeholder involvement was to minimize undue delays stemming from factors including logistic difficulties, conflicts of interest, lack of mutual availability, political influences, and lack of direct incentives. These factors represent real-world barriers to the implementation of the ideal GRADE-ADOLOPMENT process, especially in LMICs like Pakistan. Moreover, prior experience in developing such CPGs enabled the CCBP team to remain mindful of the needs and values of these groups to a large extent. Future efforts may include the development of ‘post-hoc’ additions from these stakeholders to be incorporated into future addendums or iterations of the DM guidelines.

Moreover, while the benefits of early screening for T2DM in Pakistan are numerous, the feasibility of such practice remains to be seen with particular concern for rural implementation. Rural locations in Pakistan often lack the infrastructure and healthcare facilities needed to provide screening services. Similar logistical hurdles were the basis for excluding several of the guidelines from the parent CPGs. For instance, the recommendation to prescribe glucagon for patients at risk of episodes of hypoglycemia, a life-saving medical standard in developed countries, was excluded due to the lack of availability of glucagon in Pakistan. Financial hurdles hinder the feasibility of widespread use of CGM devices in a similar fashion. Thus, implementing screening for patients above the age of 30 years can be a challenge for Pakistan’s health sector. Low accessibility, whether physical or in a financial sense, also adds to difficulties experienced by patients. Given the LMIC context of Pakistan, and a general lack of awareness of the morbidity and mortality associated with T2DM, convincing individuals to participate actively in screening may prove challenging, even if the exercise is cost-saving to patients in the long term.

This paper reports the adoloped T2DM CPG for adults in Pakistan, which was developed using a transparent and rigorous methodology which we have documented. The CPG recommends screening for T2DM above the age of 30 years, which is a modification from its source guideline by the American Diabetes Association. This lower cut-off for age at which screening should be initiated, is justified primarily by the high prevalence of T2DM amongst younger individuals in South Asia, particularly Pakistan. 18 recommendations in the source document were excluded, either because they pertained to pediatric or inpatient recommendations, or due to unavailability of certain drugs in Pakistan, or the lack of private insurance. General Practitioners in Pakistan can implement these guidelines in their practices knowing they are applicable to the local setting based on sound evidence. The nationwide implementation of the adoloped guidelines will make T2DM care more context-specific and equitable. Furthermore, groups in similar settings may review our methodology and process to adopt a similar approach to developing CPGs suitable for their local health systems. Future research should explore the effectiveness of earlier T2DM screening in a Pakistani population.

The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding author.

MQM, NAR, AS, NJ, AK, NR, SF, MAM, SA, AH, and SN were involved in the conceptualization and creation of the adoloped evidence-based clinical practice guideline. RM, OM, AP and SN were involved in the conceptualization of the manuscript and writing of its first draft. All authors contributed to the article and approved the submitted version.